Automatic closed-loop control adjustments and infusion systems incorporating same

ABSTRACT

Infusion systems, infusion devices, and related operating methods are provided. An exemplary method of operating an infusion device capable of delivering fluid to a user involves identifying a condition of the user that is likely to influence a response to the fluid in the body of the user and classifying the condition as a first type of a plurality of types of conditions. After classifying the condition as the first type, the method continues by adjusting control information for operating the infusion device based on the first type and operating the infusion device to deliver the fluid to the user in accordance with the adjusted control information.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.14/174,501, filed Feb. 6, 2014.

TECHNICAL FIELD

Embodiments of the subject matter described herein relate generally tomedical devices, and more particularly, embodiments of the subjectmatter relate to adjusting information used in providing closed-loopcontrol of a fluid infusion device to account for events that affect auser's sensitivity to the fluid being administered.

BACKGROUND

Infusion pump devices and systems are relatively well known in themedical arts, for use in delivering or dispensing an agent, such asinsulin or another prescribed medication, to a patient. A typicalinfusion pump includes a pump drive system which typically includes asmall motor and drive train components that convert rotational motormotion to a translational displacement of a plunger (or stopper) in areservoir that delivers medication from the reservoir to the body of auser via a fluid path created between the reservoir and the body of auser. Use of infusion pump therapy has been increasing, especially fordelivering insulin for diabetics.

Continuous insulin infusion provides greater control of a diabetic'scondition, and hence, control schemes are being developed that allowinsulin infusion pumps to monitor and regulate a user's blood glucoselevel in a substantially continuous and autonomous manner, for example,overnight while the user is sleeping. Regulating blood glucose level iscomplicated by variations in the response time for the type of insulinbeing used along with each user's individual insulin response.Furthermore, a user's daily activities and experiences may cause thatuser's insulin response to vary throughout the course of a day or fromone day to the next. Thus, it is desirable to account for theanticipated variations or fluctuations in the user's insulin responsecaused by the particular condition(s) experienced by the user. However,detecting the particular type of condition that the user is or has beenexperiencing is complicated by the fact that conditions having oppositeeffects on the user's insulin response could present themselves in thesame way. For example, two different conditions experienced by the usercould result in the same heart rate being exhibited by the user, buthave opposite effects on the user's insulin response.

BRIEF SUMMARY

An embodiment of a method of operating an infusion device capable ofdelivering fluid to a user is provided. An exemplary method involvesidentifying a condition of the user that is likely to influence aresponse to the fluid in the body of the user and classifying thecondition as a first type of a plurality of types of possible conditionsin the body of the user. After classifying the condition, the methodcontinues by adjusting control information for operating the infusiondevice based on the classified first type and operating the infusiondevice to deliver the fluid to the user in accordance with the adjustedcontrol information.

In one embodiment, an infusion system is provided that includes a motoroperable to deliver fluid to a user that is capable of influencing afirst condition of the user, a sensing arrangement to obtain a measuredvalue indicative of the first condition of the user, and a controlsystem coupled to the motor and the sensing arrangement. The controlsystem is configured to identify a second condition of the user that islikely to influence a response to the fluid in a body of the user,classify the second condition as a first type of a plurality of types ofconditions, and after classifying the second condition as the firsttype, adjust control information for operating the motor based on thefirst type and operate the motor to deliver the fluid to the user basedat least in part on the adjusted control information and a differencebetween a target value for the first condition of the user and themeasured value.

In another embodiment, a method of operating an infusion device capableof delivering insulin to a user involves obtaining heart ratemeasurement data for the user, identifying an insulin sensitivitycondition based on the heart rate measurement data, obtaining anactivity metric for the user, and classifying the insulin sensitivitycondition as a first type of a plurality of types of insulin sensitivityconditions based on the activity metric. After classifying the conditionas the first type, the method continues by automatically adjustingcontrol information for operating the infusion device based on the firsttype, determining delivery commands for operating a motor of theinfusion device in accordance with the adjusted control information, andoperating the motor to deliver the insulin to the user in accordancewith the delivery commands.

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the detaileddescription. This summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used as an aid in determining the scope of the claimed subjectmatter.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the subject matter may be derived byreferring to the detailed description and claims when considered inconjunction with the following figures, wherein like reference numbersrefer to similar elements throughout the figures, which may beillustrated for simplicity and clarity and are not necessarily drawn toscale.

FIG. 1 depicts an exemplary embodiment of an infusion system;

FIG. 2 is a perspective view of an exemplary embodiment of a fluidinfusion device suitable for use in the infusion system of FIG. 1;

FIG. 3 is a perspective view that depicts the internal structure of thedurable housing of the fluid infusion device shown in FIG. 2;

FIG. 4 is a block diagram of a closed-loop infusion system suitable foruse with the infusion system of FIG. 1;

FIG. 5 is a block diagram that illustrates processing modules andalgorithms of an exemplary embodiment of a control system suitable foruse with the closed-loop infusion system of FIG. 4;

FIG. 6 is a flow diagram of an exemplary control process suitable foruse with the control system of FIG. 5;

FIG. 7 is a block diagram of an exemplary infusion system suitable foruse with the closed-loop infusion system of FIGS. 4-6

FIG. 8 is a block diagram of an exemplary pump control system suitablefor use in the infusion system of FIG. 7;

FIG. 9 is a flow diagram of an exemplary closed-loop control adjustmentprocess; and

FIG. 10 is a flow diagram of an exemplary detection process suitable foruse with the closed-loop control adjustment process of FIG. 9.

DETAILED DESCRIPTION

The following detailed description is merely illustrative in nature andis not intended to limit the embodiments of the subject matter or theapplication and uses of such embodiments. As used herein, the word“exemplary” means “serving as an example, instance, or illustration.”Any implementation described herein as exemplary is not necessarily tobe construed as preferred or advantageous over other implementations.Furthermore, there is no intention to be bound by any expressed orimplied theory presented in the preceding technical field, background,brief summary or the following detailed description.

While the subject matter described herein can be implemented in anyelectronic device that includes a motor, exemplary embodiments describedbelow are implemented in the form of medical devices, such as portableelectronic medical devices. Although many different applications arepossible, the following description focuses on a fluid infusion device(or infusion pump) as part of an infusion system deployment. For thesake of brevity, conventional techniques related to infusion systemoperation, insulin pump and/or infusion set operation, and otherfunctional aspects of the systems (and the individual operatingcomponents of the systems) may not be described in detail here. Examplesof infusion pumps may be of the type described in, but not limited to,U.S. Pat. Nos. 4,562,751; 4,685,903; 5,080,653; 5,505,709; 5,097,122;6,485,465; 6,554,798; 6,558,320; 6,558,351; 6,641,533; 6,659,980;6,752,787; 6,817,990; 6,932,584; and 7,621,893; each of which are hereinincorporated by reference.

Embodiments of the subject matter described herein generally relate tofluid infusion devices including a motor that is operable to linearlydisplace a plunger (or stopper) of a reservoir provided within the fluidinfusion device to deliver a dosage of fluid, such as insulin, to thebody of a user. Delivery commands (or dosage commands) that governoperation of the motor are determined based on a difference between ameasured value for a condition in the body of the user and a targetvalue using closed-loop control to regulate the measured value to thetarget value. As described in greater detail below in the context ofFIGS. 7-10, another condition of the user that is likely to influencethe user's response (or sensitivity) to the fluid being administered isdetected and identified or otherwise classified as a particular type ofcondition from among plurality of types of conditions that couldinfluence the user's response to the fluid. Thereafter, at least some ofthe control information utilized by the closed-loop control to generatedelivery commands and operate the infusion device are automaticallyadjusted based on that particular type of condition to account for theanticipated change in the user's response to the fluid. As a result, theclosed-loop control utilizes the adjusted control information togenerate delivery commands and operate the infusion device in accordancewith the adjusted control information.

In exemplary embodiments, delivery commands for operating an insulininfusion device are determined based on a difference between a measuredblood glucose value from the body of the user and a target blood glucosevalue by applying proportional-integral-derivative (PID) closed-loopcontrol to regulate the measured value to the target value. In thisregard, the proportional, integral, and derivative gain coefficients arerespectively applied to the difference before performing the respectiveintegral and derivative operations and combining the proportional,integral, and derivative components to arrive at a delivery command foroperating a motor to deliver insulin to the body of the user. Heart ratemeasurement data for the user is obtained, and based on the heart ratemeasurement data, a condition of the user that is likely to influencethe user's insulin response (or insulin sensitivity) is detected. Anactivity metric associated with the body of the user is calculated,determined, or otherwise obtained (e.g., using acceleration measurementdata from an acceleration sensing arrangement) and utilized to classifythe detected condition as being exercise or stress.

In response to detecting and identifying exercise, one or more of thePID gain coefficients are automatically decreased to account for ananticipated increase in the user's insulin sensitivity (e.g., a fasterinsulin response). In some embodiments, amount of the decrease may bebased at least in part on the duration and/or the intensity of theexercise. Conversely, in response to detecting and identifying stress,one or more of the PID gain coefficients may be automatically increasedto account for an anticipated increase in the user's insulin resistance(e.g., a slower insulin response). Similarly, the amount of the increasemay be based at least in part on the duration and/or the intensity ofthe stress. Thereafter, the one or more adjusted PID gain coefficientsare applied to subsequent differences between measured blood glucosevalues from the body of the user and the target blood glucose value toregulate the user's blood glucose in accordance with the adjusted PIDgain coefficient(s).

In various embodiments, in addition or in alternative to adjusting oneor more PID gain coefficients, one or more additional control parametersor other control information utilized to implement the closed-loopcontrol may also be automatically adjusted to account for the detectedexercise or stress. For example, one or more limits on the insulininfusion utilized by the closed-loop control as a safeguard whengenerating the delivery commands may automatically be adjusted toaccount for the anticipated change in the user's insulin response. Inthe case of exercise or another condition where the user's insulinsensitivity increases (or insulin response time decreases), an upperlimit on the insulin infusion rate may be automatically reduced ordecreased to prevent inadvertent overdelivery. Similarly, in the case ofstress or another condition where the user's insulin resistanceincreases (or insulin response time increases), an upper limit on theinsulin infusion rate may be automatically increased to account for theincreased insulin resistance. Furthermore, in some embodiments, a targetglucose setpoint value used by the PID control may also be adjusted(e.g., increased in the case of exercise or decreased in the case ofstress) from its normal (or unadjusted) value to account for changes inthe user's insulin response in addition to or in lieu of adjusting thePID gain coefficient(s). Various other control information or controlparameters utilized for providing closed-loop control (e.g., one or moretime limit(s), glucose setpoint(s), or the like) may also be adjusted tobest account for the anticipated effect of the detected exercise orstress on the user throughout the duration of time during whichclosed-loop control is being provided.

Turning now to FIG. 1, one exemplary embodiment of an infusion system100 includes, without limitation, a fluid infusion device (or infusionpump) 102, a sensing arrangement 104, a command control device (CCD)106, and a computer 108. The components of an infusion system 100 may berealized using different platforms, designs, and configurations, and theembodiment shown in FIG. 1 is not exhaustive or limiting. In practice,the infusion device 102 and the sensing arrangement 104 are secured atdesired locations on the body of a user (or patient), as illustrated inFIG. 1. In this regard, the locations at which the infusion device 102and the sensing arrangement 104 are secured to the body of the user inFIG. 1 are provided only as a representative, non-limiting, example. Theelements of the infusion system 100 may be similar to those described inU.S. patent application Ser. No. 13/049,803, the subject matter of whichis hereby incorporated by reference in its entirety.

In the illustrated embodiment of FIG. 1, the infusion device 102 isdesigned as a portable medical device suitable for infusing a fluid, aliquid, a gel, or other agent into the body of a user. In exemplaryembodiments, the infused fluid is insulin, although many other fluidsmay be administered through infusion such as, but not limited to, HIVdrugs, drugs to treat pulmonary hypertension, iron chelation drugs, painmedications, anti-cancer treatments, medications, vitamins, hormones, orthe like. In some embodiments, the fluid may include a nutritionalsupplement, a dye, a tracing medium, a saline medium, a hydrationmedium, or the like.

The sensing arrangement 104 generally represents the components of theinfusion system 100 configured to sense, detect, measure or otherwisequantify a condition of the user, and may include a sensor, a monitor,or the like, for providing data indicative of the condition that issensed, detected, measured or otherwise monitored by the sensingarrangement. In this regard, the sensing arrangement 104 may includeelectronics and enzymes reactive to a biological condition, such as ablood glucose level, or the like, of the user, and provide dataindicative of the blood glucose level to the infusion device 102, theCCD 106 and/or the computer 108. For example, the infusion device 102,the CCD 106 and/or the computer 108 may include a display for presentinginformation or data to the user based on the sensor data received fromthe sensing arrangement 104, such as, for example, a current glucoselevel of the user, a graph or chart of the user's glucose level versustime, device status indicators, alert messages, or the like. In otherembodiments, the infusion device 102, the CCD 106 and/or the computer108 may include electronics and software that are configured to analyzesensor data and operate the infusion device 102 to deliver fluid to thebody of the user based on the sensor data and/or preprogrammed deliveryroutines. Thus, in exemplary embodiments, one or more of the infusiondevice 102, the sensing arrangement 104, the CCD 106, and/or thecomputer 108 includes a transmitter, a receiver, and/or othertransceiver electronics that allow for communication with othercomponents of the infusion system 100, so that the sensing arrangement104 may transmit sensor data or monitor data to one or more of theinfusion device 102, the CCD 106 and/or the computer 108.

Still referring to FIG. 1, in various embodiments, the sensingarrangement 104 may be secured to the body of the user or embedded inthe body of the user at a location that is remote from the location atwhich the infusion device 102 is secured to the body of the user. Invarious other embodiments, the sensing arrangement 104 may beincorporated within the infusion device 102. In other embodiments, thesensing arrangement 104 may be separate and apart from the infusiondevice 102, and may be, for example, part of the CCD 106. In suchembodiments, the sensing arrangement 104 may be configured to receive abiological sample, analyte, or the like, to measure a condition of theuser.

As described above, in some embodiments, the CCD 106 and/or the computer108 may include electronics and other components configured to performprocessing, delivery routine storage, and to control the infusion device102 in a manner that is influenced by sensor data measured by and/orreceived from the sensing arrangement 104. By including controlfunctions in the CCD 106 and/or the computer 108, the infusion device102 may be made with more simplified electronics. However, in otherembodiments, the infusion device 102 may include all control functions,and may operate without the CCD 106 and/or the computer 108. In variousembodiments, the CCD 106 may be a portable electronic device. Inaddition, in various embodiments, the infusion device 102 and/or thesensing arrangement 104 may be configured to transmit data to the CCD106 and/or the computer 108 for display or processing of the data by theCCD 106 and/or the computer 108.

In some embodiments, the CCD 106 and/or the computer 108 may provideinformation to the user that facilitates the user's subsequent use ofthe infusion device 102. For example, the CCD 106 may provideinformation to the user to allow the user to determine the rate or doseof medication to be administered into the user's body. In otherembodiments, the CCD 106 may provide information to the infusion device102 to autonomously control the rate or dose of medication administeredinto the body of the user. In some embodiments, the sensing arrangement104 may be integrated into the CCD 106. Such embodiments may allow theuser to monitor a condition by providing, for example, a sample of hisor her blood to the sensing arrangement 104 to assess his or hercondition. In some embodiments, the sensing arrangement 104 and the CCD106 may be used for determining glucose levels in the blood and/or bodyfluids of the user without the use of, or necessity of, a wire or cableconnection between the infusion device 102 and the sensing arrangement104 and/or the CCD 106.

In some embodiments, the sensing arrangement 104 and/or the infusiondevice 102 are cooperatively configured to utilize a closed-loop systemfor delivering fluid to the user. Examples of sensing devices and/orinfusion pumps utilizing closed-loop systems may be found at, but arenot limited to, the following U.S. Pat. Nos. 6,088,608, 6,119,028,6,589,229, 6,740,072, 6,827,702, 7,323,142, and 7,402,153 or U.S. patentapplication Ser. No. 13/966,120, all of which are incorporated herein byreference in their entirety. In such embodiments, the sensingarrangement 104 is configured to sense or measure a condition of theuser, such as, blood glucose level or the like. The infusion device 102is configured to deliver fluid in response to the condition sensed bythe sensing arrangement 104. In turn, the sensing arrangement 104continues to sense or otherwise quantify a current condition of theuser, thereby allowing the infusion device 102 to deliver fluidcontinuously in response to the condition currently (or most recently)sensed by the sensing arrangement 104 indefinitely. In some embodiments,the sensing arrangement 104 and/or the infusion device 102 may beconfigured to utilize the closed-loop system only for a portion of theday, for example only when the user is asleep or awake.

FIGS. 2-3 depict an exemplary embodiment of a fluid infusion device 200suitable for use as the infusion device 102 in the infusion system 100of FIG. 1. FIGS. 2-3 depict perspective views of the fluid infusiondevice 200, which includes a durable housing 202 and a base plate 204.While FIG. 2 depicts the durable housing 202 and the base plate 204 asbeing coupled together, in practice, the durable housing 202 and/or thebase plate 204 may include features, structures, or elements tofacilitate removable coupling (e.g., pawls, latches, rails, slots,keyways, buttons, or the like) and accommodate a removable/replaceablefluid reservoir 206. As illustrated in FIG. 3, in exemplary embodiments,the fluid reservoir 206 mates with, and is received by, the durablehousing 202. In alternate embodiments, the fluid reservoir 206 mateswith, and is received by, the base plate 204.

In exemplary embodiments, the base plate 204 is temporarily adhered tothe skin of the user, as illustrated in FIG. 1 using, for example, anadhesive layer of material. After the base plate 204 is affixed to theskin of the user, a suitably configured insertion device or apparatusmay be used to insert a fluid delivery needle or cannula 208 into thebody of the user. The cannula 208 functions as one part of the fluiddelivery path associated with the fluid infusion device 200. The durablehousing 202 receives the fluid reservoir 206 and retains the fluidreservoir 206 in a substantially fixed position and orientation withrespect to the durable housing 202 and the base place 204 while thedurable housing 202 and the base plate 204 are coupled. The durablehousing 202 is configured to secure to the base plate 204 in a specifiedorientation to engage the fluid reservoir 206 with a reservoir portreceptacle formed in the durable housing 202. In particular embodiments,the fluid infusion device 200 includes certain features to orient,align, and position the durable housing 202 relative to the base plate204 such that when the two components are coupled together, the fluidreservoir 206 is urged into the reservoir port receptacle to engage asealing assembly and establish a fluid seal.

In exemplary embodiments, the fluid reservoir 206 includes a fluiddelivery port 210 that cooperates with the reservoir port receptacle toestablish a fluid delivery path. In this regard, the fluid delivery port210 has an interior 211 defined therein that is shaped, sized, andotherwise configured to receive a sealing element when the fluidreservoir 206 is engaged with the reservoir port receptacle on baseplate 204. The sealing element forms part of a sealing assembly for thefluid infusion device 200 and preferably includes one or more sealingelements and/or fluid delivery needles configured to establish fluidcommunication from the interior of the reservoir 206 to the cannula 208via the fluid delivery port 210 and a mounting cap 212, and therebyestablish a fluid delivery path from the reservoir 206 to the user viathe cannula 208. In the illustrated embodiment, the fluid reservoir 206includes a second fluid port for receiving fluid. For example, thesecond fluid port 213 may include a pierceable septum, a vented opening,or the like to accommodate filling (or refilling) of the fluid reservoir206 by the patient, a doctor, a caregiver, or the like.

As illustrated in FIG. 3, the reservoir 206 includes a barrel 220 forcontaining fluid and a plunger 222 (or stopper) positioned to push fluidfrom inside the barrel 220 of the reservoir 206 along the fluid paththrough the cannula 208 to the user. A shaft 224 is mechanically coupledto or otherwise engages the plunger 222, and the shaft 224 has exposedteeth 225 that are configured to mechanically couple or otherwise engagethe shaft 224 with a gear 238 of a drive system 230 contained in thedurable housing 202. In this regard, the shaft 224 functions as a rackgear as part of a rack and pinion gear configuration. Although thesubject matter may be described herein in the context of the shaft 224being integral with or otherwise part of the plunger 222, in practice,the shaft 224 and the plunger 222 may be provided separately.

Various aspects of the motor drive system 230 may be similar to thosedescribed in U.S. patent application Ser. No. 13/049,803. The drivesystem 230 includes a motor 232 having a rotor that is mechanicallycoupled to a gear assembly 236 that translates rotation of the rotor totranslational displacement the plunger 222 in the direction 250 of thefluid delivery port 210 to deliver fluid from the reservoir 206 to auser. Accordingly, the direction 250 may alternatively be referred toherein as the fluid delivery direction 250.

In exemplary embodiments, the motor 232 is realized as a DC motor, suchas a stepper motor or brushless DC motor capable of preciselycontrolling the amount of displacement of the plunger 222 duringoperation of the infusion device 200. In exemplary embodiments, therotor of the motor 232 is mechanically coupled to a rotary shaft, which,in turn, is mechanically coupled to a first gear of the gear assembly236. For example, the first gear may be coaxial and/or concentric to anddisposed about the rotary shaft, where the first gear is affixed to orotherwise integrated with the rotary shaft such that the first gear andthe rotary shaft rotate in unison. The gear assembly 236 also includes apinion gear 238 having exposed teeth 239 that are configured to matewith or otherwise engage the exposed teeth 225 on the shaft 224 when thereservoir 206 is seated in the durable housing 202, such that rotationor displacement of the pinion gear 238 in rotational delivery direction350 produces a corresponding translational displacement of the shaft 224and/or plunger 222 in the fluid delivery direction 250 to deliver fluidto the user.

During operation of the fluid infusion device 200, when the motor 232 isoperated to rotate the rotor, the rotary shaft rotates in unison withthe rotor to cause a corresponding rotation of the first gear, which, inturn, actuates the gears of the gear assembly 236 to produce acorresponding rotation or displacement of the pinion gear 238, which, inturn, displaces the shaft 224. In this manner, the rotary shafttranslates rotation (or displacement) of the rotor into a correspondingrotation (or displacement) of the gear assembly 236 such that the teeth239 of the pinion gear 238 apply force to the teeth 225 of the shaft 224of the plunger 222 in the fluid delivery direction 250 to therebydisplace the plunger 222 in the fluid delivery direction 250 anddispense, expel, or otherwise deliver fluid from the barrel 220 of thereservoir 206 to the user via the fluid delivery path provided by thecannula 208.

As described in greater detail below in the context of FIG. 7, in one ormore exemplary embodiments, a motor position sensor (or rotor positionsensor) is configured to measure, sense, or otherwise detect rotation(or displacement) of the rotary shaft and/or the rotor of the motor 232.The motor position sensor may be utilized to provide closed-loop controlof the motor 232, such as, for example, as described in U.S. patentapplication Ser. No. 13/425,174, the subject matter of which is herebyincorporated by reference in its entirety. In exemplary embodiments, therotary shaft includes, is coupled to, or is otherwise associated with adetectable feature that is measurable or otherwise detectable by themotor position sensor. In this regard, the detectable feature may rotatein unison with the rotary shaft. In one or more embodiments, the motorposition sensor is realized as an incremental position sensor configuredto measure, sense, or otherwise detect incremental rotations of therotary shaft and/or the rotor of the motor 232. For example, inaccordance with one or more embodiments, the motor position sensor isrealized as a rotary encoder.

FIG. 4 depicts an exemplary embodiment of a closed-loop infusion system400 suitable for use with or implementation by the infusion system 100for regulating the rate of fluid infusion into a body of a user (e.g.,by infusion device 102) based on feedback from an analyte concentrationmeasurement taken from the body (e.g., via sensing arrangement 104). Inexemplary embodiments, the infusion system 400 regulates the rate ofinsulin infusion into the body of a user based on a glucoseconcentration measurement taken from the body. In preferred embodiments,the infusion system 400 is designed to model a pancreatic beta cell(β-cell). In other words, the system controls the infusion device 102 torelease insulin into a body of a user in a similar concentration profileas would be created by fully functioning human β-cells when respondingto changes in blood glucose concentrations in the body. Thus, theinfusion system 400 simulates the body's natural insulin response toblood glucose levels and not only makes efficient use of insulin, butalso accounts for other bodily functions as well since insulin has bothmetabolic and mitogenic effects. However, the algorithms must model theβ-cells closely, since algorithms that are designed to minimize glucoseexcursions in the body, without regard for how much insulin isdelivered, may cause excessive weight gain, hypertension, andatherosclerosis. Thus, in some embodiments, the infusion system 400 isintended to emulate the in vivo insulin secretion pattern and to adjustthis pattern consistent with the in vivo β-cell adaptation experiencedby normal healthy individuals with normal glucose tolerance (NGT).

The illustrated closed-loop infusion system 400 includes a glucosesensor system 410, a control system 412 and an insulin delivery system414. The glucose sensor system 410 (e.g., sensing arrangement 104)generates a sensor signal 416 representative of blood glucose levels 418in the body 420, and provides the sensor signal 416 to the controlsystem 412. The control system 412 receives the sensor signal 416 andgenerates commands 422 that are communicated to the insulin deliverysystem 414. The insulin delivery system 414 receives the commands 422and infuses insulin 424 into the body 420 in response to the commands422.

Generally, the glucose sensor system 410 includes a glucose sensor,sensor electrical components to provide power to the sensor and generatethe sensor signal 416, a sensor communication system to carry the sensorsignal 416 to the control system 412, and a sensor system housing forthe electrical components and the sensor communication system.

Typically, the control system 412 includes controller electricalcomponents and software to generate commands for the insulin deliverysystem 414 based on the sensor signal 416, and a controllercommunication system to receive the sensor signal 416 and carry commandsto the insulin delivery system 414. In preferred embodiments, thecontrol system 412 is housed in the infusion device housing (e.g.,housing 202), however, in alternative embodiments, the control system412 may be housed independently or in another component of an infusionsystem (e.g., the sensing arrangement 104, the CCD 106 and/or thecomputer 108).

The insulin delivery system 414 generally represents the infusion device(e.g., infusion device 102) and any other associated components forinfusing insulin 424 into the body 420 (e.g., the motor 232, the gearassembly 236, and the like). In particular embodiments, the infusiondevice includes infusion electrical components to activate an infusionmotor (e.g., motor 232) according to the commands 422, an infusioncommunication system to receive the commands 422 from the control system412, and an infusion device housing (e.g., housing 202) to hold theinfusion device.

Referring to FIGS. 1-4, in one or more exemplary embodiments, theglucose sensor system 410 samples or otherwise obtains the sensor signal416, stores the corresponding digital sensor values (Dsig) in a memoryand then periodically transmits the digital sensor values Dsig from thememory to the control system 412. The control system 412 processes thedigital sensor values Dsig and generates commands 422 for the insulindelivery system 414 to actuate the plunger 222 that forces insulin 424out of the reservoir 206 the via a fluid communication path from thereservoir to the subcutaneous tissue of the user's body 420.

In preferred embodiments, the control system 412 is designed to model apancreatic beta cell (β-cell). In other words, the control system 412commands the infusion device 102, 200 to release insulin 424 into thebody 420 at a rate that causes the insulin concentration in the blood tofollow a similar concentration profile as would be caused by fullyfunctioning human β-cells responding to blood glucose concentrations inthe body 420. In further embodiments, a “semi-closed-loop” system may beused, in which the user is prompted to confirm insulin delivery beforeany insulin is actually delivered.

Generally, the in vivo β-cell response to changes in glucose ischaracterized by “first” and “second” phase insulin responses. Thebiphasic insulin response of a β-cell can be modeled using components ofa proportional, plus integral, plus derivative (PID) controller.Accordingly, the control system 412 may be realized as a PID controllersince PID algorithms are stable for a wide variety of non-medicaldynamic systems, and PID algorithms have been found to be stable overwidely varying disturbances and changes in system dynamics.

A proportional component U_(P) and a derivative component U_(D) of thePID controller may be combined to represent a first phase insulinresponse, which lasts several minutes. An integral component U_(I) ofthe PID controller represents a second phase insulin response, which isa steady increase in insulin release under hyperglycemic clampconditions. As described in U.S. patent application Ser. No. 13/966,120,the magnitude of each component's contribution to the insulin responseis described by the following equations:Proportional Component Response: U _(P) =K _(P)(G−G _(B))Integral Component Response: U _(I) =K _(I)∫_(t0) ^(t)(G−G _(B)) dt+I_(B), andDerivative Component Response:

${U_{D} = {K_{D}\frac{dG}{dt}}},$

Where

U_(P) is the proportional component of the command sent to the insulindelivery system,

U_(I) is the integral component of the command sent to the insulindelivery system,

U_(D) is the derivative component of the command sent to the insulindelivery system,

K_(P) is a proportional gain coefficient,

K_(I) is an integral gain coefficient,

K_(D) is a derivative gain coefficient,

G is a present blood glucose level,

G_(B) is a desired basal glucose level,

t is the time that has passed since the last sensor calibration,

t₀ is the time of the last sensor calibration, and

I_(B) is a basal insulin concentration at t₀, or can also be describedas U_(I)(t₀).

As described in U.S. patent application Ser. No. 13/966,120, thecomponents of the PID controller can also be expressed in discrete form:Proportional Component Response: P _(con) ^(n) =K _(P)(SG _(f) ^(n) −G_(sp))Integral Component Response: I _(con) ^(n) =I _(con) ^(n-1) +K _(I)(SG_(f) ^(n) −G _(sp)); I _(con) ⁰ =I _(b)Derivative Component Response: D _(con) ^(n) =K _(D) dGdt _(f) ^(n)

Where K_(P), K_(I), and K_(D) are the proportional, integral, andderivative gain coefficients, SG_(f) and dGdt_(f) are the filteredsensor glucose and derivative respectively, and the superscript n refersto discrete time.

An acute insulin response is essential for preventing wide postprandialglycemic excursions. Generally, an early insulin response to a suddenincrease in glucose level results in less total insulin being needed tobring the glucose level back to a desired basal glucose level. This isbecause the infusion of insulin increases the percentage of glucose thatis taken up by the body. Infusing a large amount of insulin to increasethe percentage of glucose uptake while the glucose concentration is highresults in an efficient use of insulin. Conversely, infusing a largeamount of insulin while the glucose concentration is low results inusing a large amount of insulin to remove a relatively small amount ofglucose. In other words, a larger percentage of a big number is morethan a larger percentage of a small number. The infusion of less totalinsulin helps to avoid development of insulin resistance in the user. Aswell, first-phase insulin is thought to result in an early suppressionof hepatic glucose output.

Insulin sensitivity is not fixed and can change dramatically in a bodydepending on the amount of exercise by the body. For example, theinsulin response in an exercise-trained individual may be about one-halfof the insulin response of an NGT individual, but the glucose uptakerate for the exercise-trained individual may be virtually identical tothat of an NGT individual. Thus, an exercise-trained individual may havetwice the insulin sensitivity and half of the insulin response leadingto the same glucose uptake as an NGT individual. Not only is the firstphase insulin response reduced due to the effects of exercise, but thesecond phase insulin response has also been shown to adjust to insulinsensitivity.

In preferred embodiments, a closed loop control system may be used fordelivering insulin to a body to compensate for β-cells that performinadequately. There is a desired basal blood glucose level G_(B) foreach body. The difference between the desired basal blood glucose levelG_(B) and an estimate of the present blood glucose level G is theglucose level error G_(E) that must be corrected.

If the glucose level error G_(E) is positive (meaning that the presentestimate of the blood glucose level G is higher than the desired basalblood glucose level G_(B)) then the control system 412 generates aninsulin delivery command 422 to drive the infusion device 102, 200 toprovide insulin 424 to the body 420. In terms of the control loop,glucose is considered to be positive, and therefore insulin is negative.The sensing arrangement 104, 410 senses the ISF glucose level andgenerates a sensor signal 416, which, in turn, may be filtered andcalibrated to create an estimate of the present blood glucose level. Inparticular embodiments, the estimate of the present blood glucose levelG is adjusted with correction algorithms before it is compared to thedesired basal blood glucose level G_(B) to calculate a new glucose levelerror G_(E) to start the loop again.

If the glucose level error G_(E) is negative (meaning that the presentestimate of the blood glucose level is lower than the desired basalblood glucose level G_(B)) then the control system 412 reduces or stopsthe insulin delivery depending on whether the integral componentresponse of the glucose error G_(E) is still positive.

If the glucose level error G_(E) is zero, (meaning that the presentestimate of the blood glucose level is equal to the desired basal bloodglucose level G_(B)) then the control system 412 may or may not issuecommands to infuse insulin depending on the derivative component(whether the glucose level is raising or falling) and the integralcomponent (how long and by how much glucose level has been above orbelow the basal blood glucose level G_(B)). In “semi-closed loop”embodiments, the user is prompted before the control system 412 issuesthe commands to infuse insulin. The prompts may be displayed to the useron a display, sounded to the user, or otherwise provide an indication tothe user that the system is ready to deliver insulin, for example avibration or other tactile indication. In addition, the amount ofinsulin to be delivered may be displayed, with or without otherinformation, such as the total amount infused for the day or thepotential effect on the user's blood glucose level by the insulindelivery. In response, the user may indicate that the insulin should orshould not be delivered, for example by selecting a button, key, orother input. In further embodiments, there must be at least twokeystrokes so that insulin is not delivered by accident.

FIG. 5 depicts a block diagram that illustrates processing modules andalgorithms of an exemplary embodiment of a control system 500 suitablefor use as the control system 412 in the infusion system 400 of FIG. 4,and FIG. 6 is a flow chart that illustrates an exemplary embodiment of acontrol process 600 that may be performed at least in part by thecontrol system 500 to control the insulin delivery system 414 (e.g.,motor 232).

FIG. 5 schematically depicts certain inputs and outputs of the controlsystem 500, where the parallelograms represent the inputs, the ovalsrepresent the outputs, and the rectangles represent the variousfunctional modules of the control system 500. In the context of thisdescription, a “functional module” may be any process, technique,method, algorithm, computer-executable program logic, or the like. Inthis regard, the control system 500 could be realized as any electronicdevice having a processor architecture with at least one processordevice, and at least one memory element that is cooperatively associatedwith the processor architecture. The processor architecture is suitablyconfigured to execute processor-executable instructions stored in the atleast one memory element such that the control system 500 can performthe various control operations and methods described in detail herein.Although FIG. 5 conveniently depicts a number of separate functionalmodules, it should be appreciated that the overall functionality andconfiguration of the control system 500 may be alternatively arranged,and that the functions, operations, and tasks described herein may beperformed by one or more of the modules as needed.

The host electronic device that implements the control system 500 may berealized as a monitor device for an insulin infusion device, where themonitor device and the insulin infusion device are two physicallydistinct hardware devices. In another embodiment of the system, the hostelectronic device that implements the control system 500 may be realizedas a portable wireless device, where the portable wireless device andthe insulin infusion device are two physically distinct hardwaredevices. The portable wireless device in this context may be, withoutlimitation: a mobile telephone device; a tablet computer device; alaptop computer device; a portable video game device; a digital mediaplayer device; a portable medical device; or the like. In yet othersystem embodiments, the host electronic device and the insulin infusiondevice are physically and functionally integrated into a single hardwaredevice. In such embodiments, the insulin infusion device will includethe functionality of the control system 500 as presented here.

Certain embodiments of the control system 500 include a plurality ofcooperating functional modules that are designed and configured todetermine the insulin dose to be delivered to keep the patient at thetarget glucose setpoint during an overnight closed-loop operating mode.In this regard, the illustrated embodiment of the control system 500 mayinclude the following functional modules, without limitation: aclosed-loop initiation module 502; a start-up module 504; a proportionalintegral derivative insulin feedback (PID-IFB) control module 506; aninsulin limit module 508; an insulin on board (IOB) compensation module510; an insulin delivery timeout module 512; a model supervisor module514; and a missed transmission module 516.

Referring to FIG. 6, the control process 600 may begin at any time whenit is desired to enter the closed-loop operating mode. Accordingly, thecontrol process 600 may begin in response to a user-initiated command,automatically in response to the detection of operating conditions thatare usually indicative of closed-loop operation (e.g., sleeping), or thelike. Certain embodiments of the control process 600 may begin with oneor more system checks (task 602) to confirm whether or not the system isallowed to enter the closed-loop operating mode. This particular exampleemploys a sensor calibration check before allowing the system to proceedto the closed-loop mode. Referring to FIG. 5, the closed-loop initiationmodule 502 may be involved during task 602.

In some embodiments, the closed-loop initiation module 502 may considercertain sensor performance criteria that prevents closed-loopinitiation. Such criteria may include, without limitation: (1) duringstart-up when the calibration is not stable; (2) when the sensorsensitivity changes significantly; (3) when sensors may be calibratedwith a potentially invalid meter reading thereby changing the sensorsensitivity significantly; (4) any other situation that could cause amismatch between the sensor and meter for a number of most recentcalibrations spaced over a designated period of time (e.g., the two mostrecent calibrations).

The illustrated embodiment of the closed-loop initiation module 502receives at least the following items as inputs: a meter (measured) BGvalue 520; at least one sensor calibration factor 522 (i.e., calibrationmeasurements, calibration data, etc.); the sensor Isig value 524; andtimestamp data 526 that indicates the calibration time associated withthe BG value 520 and the sensor calibration factor 522. Some or all ofthis input data may be provided directly or indirectly by the insulindelivery system 414 (see FIG. 4), a translator device, a monitor device,or any device in the closed-loop system. This description assumes that anew sensor calibration factor 522 and new timestamp data 526 isgenerated for each measured BG value 520, wherein the sensor calibrationfactor 522 is associated with the calibration of the glucose sensorsystem 410 (see FIG. 4) that is being used to monitor the patient. Inparticular, the sensor calibration factor may be based on the meter BGvalue 520 and the corresponding sensor Isig value 524.

The closed-loop initiation module 502 analyzes the input data (bothcurrent values and historical values) to determine whether or not thesystem is allowed to enter into the closed-loop mode. For example, theclosed-loop initiation module 502 may: check the period between twoconsecutive calibration timestamp values; compare recent and priorcalibration factor values; and the like. The “outputs” of theclosed-loop initiation module 502 correspond to two operating modes ofthe system. More specifically, the closed-loop initiation module 502controls whether the system remains operating in the open-loop mode 528or whether the system starts the closed-loop mode 530.

Referring to FIG. 6, if the closed-loop mode is not permitted (the “No”branch of query task 604), then the control process 600 operates thesystem such that it remains in the open-loop mode (task 606). On theother hand, if the closed-loop mode is permitted (the “Yes” branch ofquery task 604), then the control process 600 can initiate and start theclosed-loop mode in an appropriate manner (task 608). Referring again toFIG. 5, a correction bolus 532 can be calculated and delivered (ifneeded) to mitigate hyperglycemia at the commencement of the closed-loopmode. This correction bolus 532 serves as an additional safeguard toachieve a target blood glucose level if a measured meter reading isgreater than a threshold value. If the control process 600 determinesthat a correction bolus is required, then an appropriate insulin doseinstruction is generated for execution by the insulin delivery system atthe outset of the closed-loop mode.

Referring to FIG. 5, the start-up module 504 may be called in responseto a determination that the system can proceed to the closed-loopoperating mode. Once the system is in the closed-loop mode, thecontroller retrieves historical data that can be processed and used asdescribed in more detail below. In one or more embodiments, for example,the controller obtains data for the last 24 hours (from the insulindelivery system, from a monitor, or the like). Thereafter, thecontroller retrieves data packets once every sampling period to obtain,without limitation: sensor glucose (SG) values; sensor Isig values;sensor calibration factors; information related to the amount of insulindelivered; information related to manual boluses delivered; and sensorcalibration factors. As explained in more detail below, the receivedinformation can be used in the various safeguards, and to determine thefinal insulin dose.

The start-up module 504 receives sensor glucose (SG) values 540 as aninput, and the functionality of the start-up module 504 may be initiatedin response to the start of the closed-loop mode 530 (this triggermechanism is represented by the dashed arrow 542 in FIG. 5). The SGvalues 540 may be provided directly by the glucose sensor system 410 orindirectly via the insulin delivery system 414, a translator device, orany device in the closed-loop system (see FIG. 4). This descriptionassumes that SG values 540 are received by the start-up module 504 in anongoing manner as they become available. The start-up module 504 mayalso utilize a target glucose setpoint value 544, which may beinternally maintained, generated, and/or provided by the control system500. For the implementation presented here, the target glucose setpointvalue 544 represents a fixed (constant) value that the user can specify(FIG. 5 depicts the target glucose setpoint value 544 in dashed lines toindicate that the value is a user-specified parameter rather than afunctional module or data received by the system).

In certain embodiments, the start-up module 504 calculates a finaltarget glucose value 546, which serves as an input to the PID-IFBcontrol module 506. The final target glucose value 546 enables thesystem to make a smoother transition between open-loop and closed-loopmodes (by gradually adjusting the final target glucose value 546). Thestart-up module 504 may utilize the target glucose setpoint value 544 tocalculate the final target glucose value 546. In this regard, thestart-up module 504 elevates the final target glucose value 546 to thesame level as the sensor glucose value at the start of the closed-loopmode, provided the sensor glucose is above a certain threshold. As timeprogresses, the final target glucose value 546 gradually decreases backto the target glucose setpoint value 544 (usually in approximately twohours). Referring to FIG. 6, the control process 600 calculates thefinal target glucose value (task 610) and continues by calculating anuncompensated insulin infusion rate, PIDRate(n), based at least in parton the final target glucose value (task 612). For this example, thestart-up module 504 may be involved during task 610, and the PID-IFBcontrol module 506 may be involved during task 612.

As an additional safeguard, the insulin limit module 508 cooperates withthe PID-IFB control module 506 to provide an upper insulin limit that iscalculated based on the patient's insulin intake during a designatedfasting period, the patient's fasting blood glucose, and the patient'sinsulin sensitivity. This insulin limit imposes an upper limit to theinsulin delivery rate to avoid over-delivery of insulin by the systemdue to potential sensor error.

The PID-IFB control module 506 may be configured to carry out thecontrol processes described above with reference to FIG. 4. In someembodiments, the PID-IFB control module 506 receives at least thefollowing items as inputs: the SG value 540 (which may be used tocalculate a rate of change value that indicates the rate of change ofthe SG value); the current sensor Isig value 550; the current sensorcalibration factor 552; and an amount of insulin delivered 554. As shownin FIG. 5, the PID-IFB control module 506 may also receive an insulinlimit 559 (e.g., a maximum insulin infusion rate) for the user, ascalculated by the insulin limit module 508. The inputs to the PID-IFBcontrol module 506 may be provided directly or indirectly by the insulindelivery system 414, the glucose sensor system 410, a translator device,a monitor device, and/or any device in the closed-loop system (see FIG.4). The PID-IFB control module 506 is suitably configured to calculatethe insulin infusion rate based on the current and past SG values 540,the SG rate of change, the sensor Isig value 550, the sensor calibrationfactor 552, the final target glucose value 546, and the insulindelivered 554 in order to achieve euglycemia. These (and possibly other)values may be received by the PID-IFB control module 506 in an ongoingmanner as they become available, e.g., in five minute intervals or inaccordance with any desired schedule.

The insulin delivered 554 is a parameter or value that indicates theamount of insulin that has been delivered to the patient by the insulindelivery system. Thus, the insulin delivered 554 may indicate recentboluses (typically by Units) delivered over a period of time. In certainimplementations, the insulin delivered 554 corresponds to the amount ofinsulin delivered in the last sampling time, which may be, withoutlimitation: one minute; five minutes; thirty seconds; or any designatedsampling time. The insulin delivered 554 may also indicate the amount ofinsulin delivered by the delivery system as basal or boluses in anydefined period of time in the past (e.g., the last N hours) or theamount of insulin delivered by the system in the last sampling cycle. Inpractice, the PID-IFB control module 506 (and the IOB compensationmodule 510) may be “initialized” to collect and save historical valuesfor the insulin delivered 554 as needed. Thereafter, the insulindelivered 554 can simply indicate an amount of insulin administered bythe system during the last sampling time period if by a bolus or basalchannels.

As mentioned above, the PID-IFB control module 506 may utilize the upperinsulin limit 559, which is a patient-specific parameter. In certainembodiments, the upper insulin limit 559 may be entered by the user, acaregiver, or the like. Alternatively, the insulin limit module 508 maybe responsible for calculating or otherwise managing the upper insulinlimit 559 if so desired. The upper insulin limit 559 imposes an upperlimit to the insulin delivery rate as an additional safety feature toavoid over-delivery of insulin by the control system 500 due topotential sensor error. Thus, if the PID-IFB control module 506recommends a dose higher than the insulin limit 559, the insulin limit559 will be utilized to constrain the insulin delivered to the insulinlimit value. In addition, implementation of the insulin limit 559 will“freeze” the integral component of the PID to its previous value toprevent integral windup, which can cause continuous integrating of theglucose error until it reaches maximum values. In certain embodiments,the upper insulin limit 559 has a default value set at five times thepatient's basal rate. Hence, if the maximum value is reached, thePID-IFB control algorithm will be fairly aggressive in calculating aninsulin dose. Accordingly, to minimize integral windup, the insulinlimit 559 is fed back to the PID-IFB control module 506 (as depicted inFIG. 5) for use in the next insulin dose calculation.

The PID-IFB control module 506 operates as described previously tocalculate a current insulin dose 558 as an output value (the currentinsulin dose 558 is also referred to herein as the uncompensated insulininfusion rate, PIDRate(n)). In practice, the current insulin dose 558 istypically expressed as an infusion rate (Units/Hour). In the context ofthis description, the current insulin dose 558 may represent aclosed-loop infusion rate that has already been subjected to limiting bythe insulin limit module 508, and which may be subjected to furtheradjustment or compensation by the IOB compensation module 510. Thus, theoutput of the insulin limit module 508 (the upper insulin limit 559)represents a potentially limited insulin dose to be provided by thePID-IFB control module 506—if no limit is imposed, then the insulinlimit 559 has no effect on the output of the PID-IFB control module 506;otherwise, the current insulin dose 558 will be the same as the upperinsulin limit 559. Referring again to FIG. 6, the control process 600may compensate for the insulin “on board” the patient by calculating anadjusted insulin infusion rate, AdjustedRate(n), based at least in parton the uncompensated insulin infusion rate (task 614). For this example,the IOB compensation module 510 may be involved during task 614.

The IOB compensation module 510 receives at least the following items asinputs: the current insulin dose 558; and information regarding manualboluses delivered 560. The manual boluses delivered 560 may be provideddirectly or indirectly by the insulin delivery system 414, a translatordevice, a monitor device, and/or any device in the closed-loop system(see FIG. 4). This description assumes that the manual boluses delivered560 is received by the IOB compensation module 510 in an ongoing manneras it becomes available, e.g., in five minute intervals or in accordancewith any desired schedule. The IOB compensation module 510 is suitablyconfigured to estimate insulin on board based on manual bolusesdelivered, before or during closed-loop operation, in order tocompensate the final infusion rate to help avoid over-delivery ofinsulin by the control system 500. Accordingly, the output of the IOBcompensation module 510 may be a final insulin dose 562 expressed as afinal infusion rate (Units/Hour). The final insulin dose 562 is alsoreferred to herein as the adjusted insulin infusion rate,AdjustedRate(n).

Referring to FIG. 6, the control process 600 uses the adjusted insulininfusion rate, AdjustedRate(n), to control the insulin infusion device,which in turn regulates the delivery of insulin to the body of the user(task 616). In certain embodiments, the adjusted insulin infusion rateis communicated to the insulin infusion device in an appropriate manner(such as wireless data communication). The control process 600 maycontinue as described above in an iterative and ongoing manner tomonitor the condition of the user and deliver insulin as needed withoutuser involvement. That said, if the control process 600 determines thatthe closed-loop operating mode should be terminated (the “Yes” branch ofquery task 618), then the control process 600 causes the system toswitch back to the open-loop mode (task 620). The closed-loop mode maybe ended in response to a user-initiated command, automatically inresponse to the detection of operating conditions that are usuallyindicative of open-loop operation, or the like.

If query task 618 determines that the closed-loop mode should continue(the “No” branch of query task 618), then the control process 600 maycheck whether it is time to perform another iteration of the controlroutine. In other words, the control process 600 may check for the nextsampling time (query task 622). If it is time for the next iteration,then the control process 600 may return to task 610 and repeat thecomputations with the next set of data values. For example, the nextiteration of the control routine may obtain and process the currentvalues of some or all of the following parameters, without limitation:the SG value 540; the SG rate of change; the sensor Isig value 524; theamount of insulin delivered 554; and the manual boluses delivered 560.This allows the control process 600 to adjust the final insulin infusionrate in an ongoing manner in accordance with a predetermined schedule, adesignated sampling rate, or the like.

The insulin delivery timeout module 512 monitors if the patient isreceiving continuous delivery of insulin at the maximum insulin limit orthe minimum allowable infusion of zero Units/Hour for a time specifiedby the controller. Accordingly, the insulin delivery timeout module 512may receive the insulin delivered 554 as an input. If the specified timeis exceeded, the system will trigger a fail-safe alert 566. Otherwise,the system remains in the closed-loop operating mode 568.

Referring back to FIG. 5, the model supervisor module 514 receives atleast the following as inputs: the insulin delivered 554; sensor Isigvalues 550; and one or more sensor calibration factors 552. The inputsto the model supervisor module 514 may be provided directly orindirectly by the insulin delivery system 414, the glucose sensor system410, a translator device, a monitor device, and/or any device in theclosed-loop system (see FIG. 4). The model supervisor module 514 issuitably designed and configured to estimate the user's glucoseconcentration in real time (or substantially real time) based on theinsulin delivered 554, the sensor Isig values 550, and the sensorcalibration factors 552. The sensor calibration factors 552 used by themodel supervisor module 514 are equal to the sensor calibration factors522 used by the closed-loop initiation module 502. That said, theclosed-loop initiation module 502 utilizes the sensor calibrationfactors 522 at one particular time, whereas the model supervisor module514 considers the sensor calibration factors 552 in an ongoing andcontinuous manner during operation in the closed-loop mode. Should themodel-predicted glucose and the sensor glucose values differsignificantly, the system will exit closed loop mode. Accordingly, themodel supervisor module 514 regulates whether the system remains in theclosed-loop mode 574 or switches to the open-loop mode 576.

The missed transmission module 516 is suitably configured to monitor thefollowing, without limitation: the sensor Isig values 550; the SG values540; and the sensor calibration factors 552. More particularly, themissed transmission module 516 continuously monitors to check whetherthe system is receiving data packets that convey the necessaryinformation and input values. For missed data packets totaling less thana lower threshold of time (e.g., 15 minutes), the system remains in theclosed-loop mode, as indicated by block 580 in FIG. 5. During this time,the system will continue to calculate the insulin dose using theclosed-loop control methodology based on the last valid sensor glucosevalue. For missed data packets totaling a time longer than the lowerthreshold and shorter than an upper threshold of time (e.g., 60minutes), the missed transmission module 516 will switch the system to apre-programmed safe basal rate, as indicated by block 582 in FIG. 5. Incertain embodiments, this safe basal rate is defined as half thepatient's overnight basal rate, and this parameter may be programmed bya caregiver or physician. If the missed transmission module 516 startsreceiving data packets while the safe basal rate is being administered,the system will switch back to the closed-loop mode. For missed datapackets totaling more than the upper threshold of time, the system willswitch to the open-loop mode, as indicated by block 584 in FIG. 5. Atthis point, the system will be controlled to deliver a pre-programmedopen-loop overnight basal rate.

To summarize, the control system 500 determines whether to enter intothe closed-loop mode in response to at least the recent meter BG values520, the sensor calibration factors 522, and the calibration timestampdata 526. The control system 500 utilizes the closed-loop initiationmodule 502 to check if the sensor calibration time between the last twocalibration values is within an acceptable range, and whether any changebetween the two calibration values (recent and prior value) isacceptable. If so, the control system 500 will switch the system intothe closed-loop mode. Once the system is in the closed-loop mode, thecontrol system 500 will periodically receive data packets (e.g., everyfive minutes) that include the current SG value 540, the current sensorIsig values 550, the insulin delivered 554, the sensor calibrationfactors 552, and manual boluses delivered 560. In certain embodiments,each of the data packets received by the control system 500 includesdata collected during the previous 24-hour period.

The start-up module 504 utilizes the SG values 540 and the targetglucose setpoint value 544 to calculate the final target glucose value546. In some embodiments, the target glucose setpoint value 544 is setto 120 mg/dL, although other settings could be used if so desired (atypical range of settings may be, for example 70-300 mg/dL). Thisresults in a smoother transition between open-loop and closed-loop modesby gradually adjusting the final target glucose value 546. The finaltarget glucose value 546 is sent to the PID-IFB control module 506 foruse as one input that influences the calculation of the final insulindose 562.

The PID-IFB control module 506 utilizes the final target glucose value546, the current and past SG values 540, the SG rate of change values,and the insulin delivered 554 to determine the insulin infusion rate(the current insulin dose 558) in order to achieve euglycemia. As anadditional safeguard, the upper insulin limit 559 (calculated based onthe patient's insulin intake during a fasting period, fasting bloodglucose, and insulin sensitivity) from the insulin limit module 508 isinput into the control system 500 for each patient to impose an upperlimit to the insulin delivery rate to avoid over-delivery of insulin bythe control system 500. The PID-IFB control module 506 considers theupper insulin limit 559 before sending the current insulin dose 558 tothe IOB compensation module 510, which estimates insulin on board frommanual boluses, before or during closed-loop operation, in order tocalculate the final insulin dose 562. The final insulin dose 562 may becommunicated from the control system 500 directly or indirectly to theinsulin delivery system 414 such that the final insulin dose 562 can bedelivered to the patient during closed-loop operation.

Additional safeguards could be implemented to monitor the system duringclosed-loop operation, such that the system exits the closed-loop modewhen certain criteria are not met. For example, the control system 500may cause the system to exit the closed-loop mode if more than adesignated number of consecutive data packets are missed. This assumesthat the control system 500 usually receives data packets (from theinsulin delivery system 414, from a monitor, from a translation device,or the like) in a continuous manner during closed-loop operation. Thus,if the control system 500 detects that more than a threshold number ofconsecutive data packets are not received as expected, the system willbe commanded to exit the closed-loop mode. This functionality isassociated with the missed transmission module 516, as describedpreviously.

Moreover, the model supervisor module 514 estimates the user's glucoseconcentration in an ongoing manner, based on the insulin delivered 554,the sensor Isig values 550, and the sensor calibration factors 552. Ifthe difference between the model-predicted glucose and the sensorglucose value is greater than a stated threshold, the control system 500may cause the system to exit the closed-loop mode.

As summarized above, the control system 500 employs a number of modulesor functions that cooperate to regulate the delivery of insulin duringclosed-loop operation: the closed-loop initiation module 502; thestart-up module 504; the PID-IFB control module 506; the insulin limitmodule 508; and the IOB compensation module 510. Moreover, the controlsystem 500 may employ a number of modules that perform varioussafeguarding functions during closed-loop operation. These safeguardingmodules may include: the insulin delivery timeout module 512; the modelsupervisor module 514; and the missed transmission module 516.

FIG. 7 depicts another exemplary embodiment of an infusion system 700suitable for use with an infusion device 702, such as the infusiondevice 102 in FIG. 1 or the infusion device 200 of FIG. 2 in conjunctionwith the closed-loop infusion system 400 of FIG. 4 and the closed-loopcontrol process 600 of FIG. 6. In this regard, the illustrated infusionsystem 700 is capable of operating the infusion device 702 to control orotherwise regulate a condition in the body 701 of a user, such as theblood glucose level, to a desired (or target) value or otherwisemaintain the condition within a range of acceptable values. A sensingarrangement 704 (e.g., sensing arrangement 104) is communicativelycoupled to the infusion device 702, and in exemplary embodiments, thesensing arrangement 704 is configured to sense, detect, measure orotherwise quantify the condition being regulated in the body 701 of theuser. However, it should be noted that in alternative embodiments, thecondition being regulated by the infusion system 700 may be correlativeto the measured values obtained by the sensing arrangement 704. Thatsaid, for clarity and purposes of explanation, the subject matter may bedescribed herein in the context of the sensing arrangement 704 beingrealized as a blood glucose sensing arrangement that senses, detects,measures or otherwise quantifies the blood glucose level being regulatedin the body 701 of the user.

In exemplary embodiments, the infusion system 700 includes one or moreadditional sensing arrangements 706, 708 configured to sense, detect,measure or otherwise quantify a characteristic of the body 701 of theuser that is indicative of a condition in the body 701 of the user thatis likely to influence the response by the user's body 701 to the fluidbeing delivered. For example, in the illustrated embodiment, theinfusion system 700 includes a heart rate sensing arrangement 706 thatmay be worn on or otherwise associated with the user's body 701 tosense, detect, measure or otherwise quantify the user's heart rate,which, in turn, may be indicative of exercise, stress, or some othercondition in the body 701 that is likely to influence the user's insulinresponse in the body 701. The measured heart rate values output by theheart rate sensing arrangement 706 may be utilized by the pump controlsystem 720 to calculate or otherwise quantify one or morecharacteristics of the user's heart rate, such as the user's heart ratevariability (HRV) or the like. Alternatively, the heart rate sensingarrangement 706 may sense, detect, measure or otherwise quantifycharacteristics of the user's heart rate (e.g., the user's HRV) andoutput those values in addition to measured heart rate values. While theillustrated embodiment depicts the heart rate sensing arrangement 706 asbeing realized as a standalone component worn by the user, inalternative embodiments, the heart rate sensing arrangement 706 may beintegrated with the infusion device 702 or with another sensingarrangement 704, 708 worn on the body 701 of the user.

Additionally, the illustrated infusion system 700 includes anacceleration sensing arrangement 708 (or accelerometer) that may be wornon or otherwise associated with the user's body 701 to sense, detect,measure or otherwise quantify an acceleration of the user's body 701,which, in turn, may be indicative of exercise or some other condition inthe body 701 that is likely to influence the user's insulin response. Inthe illustrated embodiment, the acceleration sensing arrangement 708 isdepicted as being integrated into the infusion device 702, however, inalternative embodiments, the acceleration sensing arrangement 708 may beintegrated with another sensing arrangement 704, 706 on the body 701 ofthe user, or the acceleration sensing arrangement 708 may be realized asa standalone component that is worn by the user.

In the illustrated embodiment, the pump control system 720 generallyrepresents the electronics and other components of the infusion device702 that control operation of the fluid infusion device 702 according toa desired infusion delivery program in a manner that is influenced bysensor data pertaining to a condition of a user (e.g., the user'scurrent glucose level) received from the glucose sensing arrangement 704and/or in a manner that is dictated by the user. To support closed-loopcontrol, the pump control system 720 maintains, receives, or otherwiseobtains a desired value for a condition in the body 701 of the user tobe regulated (e.g., a target or commanded blood glucose value). Forexample, the infusion device 702 may store or otherwise maintain thetarget value in a data storage element accessible to the pump controlsystem 720. Alternatively, the target value may be received from anexternal component (e.g., CCD 106 and/or computer 108) or be input by auser via a user interface associated with the infusion device 702.

As described in greater detail below in the context of FIGS. 9-10, inexemplary embodiments, the pump control system 720 is coupled to thesensing arrangements 706, 708 to obtain measurement data indicative ofthe respective characteristics of the body 701 of the user from therespective sensing arrangements 706, 708. Based on the measurement data,the pump control system 720 detects or otherwise identifies a conditionbeing experienced by the body 701 of the user that is likely toinfluence the user's insulin response. The pump control system 720 alsoutilizes the measurement data to identify or otherwise classify thedetected insulin sensitivity condition as a particular type of aplurality of possible types of conditions that are likely to influencethe user's insulin response. For example, based on the heart ratemeasurement data obtained from the heart rate sensing arrangement 706and the acceleration measurement data obtained from the accelerationsensing arrangement 708, the pump control system 720 may identify orotherwise determine whether the body 701 of the user is experiencingexercise or stress. Based on the identified type of insulin sensitivitycondition in the body 701, the pump control system 720 automaticallyadjusts or otherwise modifies at least some of the closed-loop controlinformation for operating the infusion device 702 in a manner thataccounts for the anticipated change in the user's insulin responselikely to be caused by the identified condition. Thereafter, the pumpcontrol system 720 operates the infusion device 702 to provideclosed-loop control in accordance with the adjusted control information.For example, as described in greater detail below, the pump controlsystem 720 may adjust one or more PID gain coefficients, one or moreinsulin delivery limits, one or more PID blood glucose targets, one ormore time limits for the closed-loop control, or the like.

Still referring to FIG. 7, the infusion device 702 includes a motorcontrol module 712 coupled to a motor 732 (e.g., motor 232) that isoperable to displace a plunger 722 (e.g., plunger 222) in a reservoir(e.g., reservoir 206) and provide a desired amount of fluid to the body701 of a user. In this regard, displacement of the plunger 722 resultsin the delivery of a fluid that is capable of influencing the conditionin the body 701 of the user to the body 701 of the user via a fluiddelivery path. A motor driver module 714 is coupled between an energysource 718 and the motor 732. The motor control module 712 is coupled tothe motor driver module 714, and the motor control module 712 generatesor otherwise provides command signals that operate the motor drivermodule 714 to provide current (or power) from the energy source 718 tothe motor 732 to displace the plunger 722 in response to receiving, froma pump control system 720, a delivery command (or dosage command)indicative of the desired amount of fluid to be delivered.

In exemplary embodiments, the energy source 718 is realized as a batteryhoused within the infusion device 702 (e.g., within housing 202) thatprovides direct current (DC) power. In this regard, the motor drivermodule 714 generally represents the combination of circuitry, hardwareand/or other electrical components configured to convert or otherwisetransfer DC power provided by the energy source 718 into alternatingelectrical signals applied to respective phases of the stator windingsof the motor 732 that result in current flowing through the statorwindings that generates a stator magnetic field and causes the rotor ofthe motor 732 to rotate. The motor control module 712 is configured toreceive or otherwise obtain a delivery command (or commanded dosage)from the pump control system 720, convert the delivery command to acommanded translational displacement of the plunger 722, and command,signal, or otherwise operate the motor driver module 714 to cause therotor of the motor 732 to rotate by an amount that produces thecommanded translational displacement of the plunger 722. For example,the motor control module 712 may determine an amount of rotation of therotor required to produce translational displacement of the plunger 722that achieves the commanded dosage received from the pump control system720.

Based on the current rotational position (or orientation) of the rotorwith respect to the stator that is indicated by the output of the rotorsensing arrangement 716, the motor control module 712 determines theappropriate sequence of alternating electrical signals to be applied tothe respective phases of the stator windings that should rotate therotor by the determined amount of rotation from its current position (ororientation). In embodiments where the motor 732 is realized as a BLDCmotor, the alternating electrical signals commutate the respectivephases of the stator windings at the appropriate orientation of therotor magnetic poles with respect to the stator and in the appropriateorder to provide a rotating stator magnetic field that rotates the rotorin the desired direction. Thereafter, the motor control module 712operates the motor driver module 714 to apply the determined alternatingelectrical signals (e.g., the command signals) to the stator windings ofthe motor 732 to achieve the desired delivery of fluid to the user. Whenthe motor control module 712 is operating the motor driver module 714,current flows from the energy source 718 through the stator windings ofthe motor 732 to produce a stator magnetic field that interacts with therotor magnetic field. In some embodiments, after the motor controlmodule 712 operates the motor driver module 714 and/or motor 732 toachieve the commanded dosage, the motor control module 712 ceasesoperating the motor driver module 714 and/or motor 732 until asubsequent delivery command is received. In this regard, the motordriver module 714 and the motor 732 enter an idle state during which themotor driver module 714 effectively disconnects or isolates the statorwindings of the motor 732 from the energy source 718. In other words,current does not flow from the energy source 718 through the statorwindings of the motor 732 when the motor 732 is idle, and thus, themotor 732 does not consume power from the energy source 718 in the idlestate, thereby improving efficiency.

Depending on the embodiment, the motor control module 712 may beimplemented or realized with a general purpose processor, amicroprocessor, a controller, a microcontroller, a state machine, acontent addressable memory, an application specific integrated circuit,a field programmable gate array, any suitable programmable logic device,discrete gate or transistor logic, discrete hardware components, or anycombination thereof, designed to perform the functions described herein.Furthermore, the steps of a method or algorithm described in connectionwith the embodiments disclosed herein may be embodied directly inhardware, in firmware, in a software module executed by the motorcontrol module 712, or in any practical combination thereof. Inexemplary embodiments, the motor control module 712 includes orotherwise accesses a data storage element or memory, including any sortof random access memory (RAM), read only memory (ROM), flash memory,registers, hard disks, removable disks, magnetic or optical massstorage, or any other short or long term storage media or othernon-transitory computer-readable medium, which is capable of storingprogramming instructions for execution by the motor control module 712.The computer-executable programming instructions, when read and executedby the motor control module 712, cause the motor control module 712 toperform the tasks, operations, functions, and processes describedherein.

It should be understood that FIG. 7 depicts a simplified representationof the infusion device 702 for purposes of explanation and is notintended to limit the subject matter described herein in any way. Inthis regard, depending on the embodiment, some features and/orfunctionality of the motor control module 712 may implemented by orotherwise integrated into the pump control system 720, or vice versa.Furthermore, some of the features and/or functionality of the pumpcontrol system 720 described herein may be implemented by a remotecomputing device that is physically distinct and/or separate from theinfusion device 702 (e.g., the CCD 106, the computer 108, and/or anothermonitor device) and communicatively coupled to the motor control module712 and/or the sensing arrangements 704, 706, 708. Additionally,although FIG. 7 depicts the glucose sensing arrangement 704 as beingphysically separate and distinct from the infusion device 702, inalternative embodiments, the glucose sensing arrangement 704 may beintegrated into or otherwise implemented by the infusion device 702(e.g., by providing the glucose sensing arrangement 704 within thehousing 202).

FIG. 8 depicts an exemplary embodiment of a pump control system 800suitable for use as the pump control system 720 in FIG. 8 in accordancewith one or more embodiments. The illustrated pump control system 800includes, without limitation, a pump control module 802, acommunications interface 804, and data storage elements 806, 808. Itshould be understood that FIG. 8 is a simplified representation of pumpcontrol system 800 for purposes of explanation and is not intended tolimit the subject matter described herein in any way. In this regard,although FIG. 8 depicts the data storage elements 806, 808 as beingdistinct or otherwise separate from one another, in practice, the datastorage elements 806, 808 may be realized using a single integrated datastorage element.

The control module 802 generally represents the hardware, circuitry,logic, firmware and/or other components of the pump control system 800configured to determine delivery (or dosage) commands for operating amotor using closed-loop control and perform various additional tasks,operations, functions and/or operations described herein. Depending onthe embodiment, the control module 802 may be implemented or realizedwith a general purpose processor, a microprocessor, a controller, amicrocontroller, a state machine, a content addressable memory, anapplication specific integrated circuit, a field programmable gatearray, any suitable programmable logic device, discrete gate ortransistor logic, discrete hardware components, or any combinationthereof, designed to perform the functions described herein.Furthermore, the steps of a method or algorithm described in connectionwith the embodiments disclosed herein may be embodied directly inhardware, in firmware, in a software module executed by the controlmodule 802, or in any practical combination thereof.

In exemplary embodiments, the data storage element (or memory) 806 isrealized as any sort of random access memory (RAM), read only memory(ROM), flash memory, registers, hard disks, removable disks, magnetic oroptical mass storage, short or long term storage media, or any othernon-transitory computer-readable medium capable of storing programminginstructions for execution by the control module 802. Thecomputer-executable programming instructions, when read and executed bythe control module 802, cause the control module 802 to perform thetasks, operations, functions, and processes described in greater detailbelow. In this regard, the control scheme or algorithm implemented bythe control module 802 may be realized as control application code thatis stored or otherwise maintained in the memory 806 and executed by thecontrol module 802 to implement or otherwise provide one or more of theclosed-loop PID control components in software. For example, the controlapplication code may be executed by the control module 802 to implementor otherwise provide one or more of the components of control system 500of FIG. 5 and implement the control process 600 of FIG. 6.

As described above with reference to FIGS. 4-7, in exemplaryembodiments, the control module 802 obtains a target blood glucose valuefor the user associated with the infusion device 702, obtains a measured(or sensed) blood glucose value from the glucose sensing arrangement704, and performs PID control to regulate the measured value to thetarget value. For example, the control module 802 may include orotherwise implement a summation block that determines a differencebetween the target blood glucose value and the measured blood glucosevalue, a proportional gain block that multiplies the difference by aproportional gain coefficient, integration and gain blocks that multiplythe integrated difference by an integration gain coefficient, andderivative and gain blocks that multiply the derivative of thedifference by a derivative gain coefficient.

In the illustrated embodiment of FIG. 8, the data storage element 808generally represents the hardware, circuitry and/or other components ofthe pump control system 720 that are configured to store the closed-loopcontrol information for the control scheme implemented by the controlmodule 802. The data storage element 808 may be realized as any sort ofrandom access memory (RAM), read only memory (ROM), flash memory,registers, hard disks, removable disks, magnetic or optical massstorage, short or long term storage media, or any other non-transitorycomputer-readable medium. That said, in exemplary embodiments, the datastorage element 808 is realized a plurality of registers associated withthe control parameters for the PID control, and accordingly, the datastorage element 808 may alternatively be referred to herein as theparameter registers. For example, a first register of the parameterregisters 808 may store the target value for the condition beingregulated, a second register of the parameter registers 808 may storethe proportional gain coefficient used by the proportional gain block, athird register of the parameter registers 808 may store the integrationgain coefficient, and a fourth register of the parameter registers 808may store the derivative gain coefficient. Additional parameterregisters 808 may also store or otherwise maintain insulin deliverylimits for the user, along with additional user-specific PID controlparameters and/or other control information referenced by the controlmodule 802 when implementing the closed-loop PID control. In thisregard, the user-specific PID control parameters may include one or moreof the following: a user-specific total daily insulin value, auser-specific insulin sensitivity value, a user-specific carbohydrateratio value, and/or other user-specific mathematical model parametervalues that characterize or otherwise describe the user's insulinsensitivity and/or meal response.

Still referring to FIG. 8, the communications interface 804 generallyrepresents the hardware, circuitry, logic, firmware and/or othercomponents configured to support communications to/from the pump controlsystem 800. For example, referring to FIGS. 1 and 7, the communicationsinterface 804 may include or otherwise be coupled to one or moretransceiver modules capable of supporting wireless communicationsbetween the infusion device 702 and another device (e.g., one or more ofthe sensing arrangements 104, 704, 706, the CCD 106, the computer 108,or the like).

FIG. 9 depicts an exemplary closed-loop control adjustment process 900suitable for implementation by a control system associated with a fluidinfusion device to automatically adjust control information used togenerate commands for operating a motor to deliver fluid to a user in amanner that accounts for a condition in the body of the user that islikely to influence the user's response to the fluid. The various tasksperformed in connection with the closed-loop control adjustment process900 may be performed by hardware, firmware, software executed byprocessing circuitry, or any combination thereof. For illustrativepurposes, the following description refers to elements mentioned abovein connection with FIGS. 1-8. In practice, portions of the closed-loopcontrol adjustment process 900 may be performed by different elements ofan infusion system, such as, for example, the infusion device 702, oneor more of the sensing arrangements 704, 706, 708, and/or the pumpcontrol system 720 in the infusion system 700 of FIG. 7. It should beappreciated that the closed-loop control adjustment process 900 mayinclude any number of additional or alternative tasks, the tasks neednot be performed in the illustrated order and/or the tasks may beperformed concurrently, and/or the closed-loop control adjustmentprocess 900 may be incorporated into a more comprehensive procedure orprocess having additional functionality not described in detail herein.Moreover, one or more of the tasks shown and described in the context ofFIG. 9 could be omitted from a practical embodiment of the closed-loopcontrol adjustment process 900 as long as the intended overallfunctionality remains intact.

In exemplary embodiments, the closed-loop control adjustment process 900initializes or otherwise begins in response to determining to enter aclosed-loop mode (e.g., closed-loop mode 530 at task 1008).Additionally, in some embodiments, the closed-loop control adjustmentprocess 900 may also be performed at the beginning of each iteration ofthe closed-loop control process (e.g., at each new sampling time at task1022) to dynamically adjust control information while the closed-loopcontrol mode is being implemented.

In the illustrated embodiment, the closed-loop control adjustmentprocess 900 begins by identifying, detecting, or otherwise determiningwhether a condition potentially affecting the user's response (orsensitivity) to the fluid being administered has occurred in the body ofthe user (task 902). In exemplary embodiments, the pump control system720, 800 monitors the outputs of the sensing arrangements 706, 708 inthe infusion system 700 to detect or otherwise identify a condition thatis likely to influence the user's insulin response (or sensitivity),such as exercise, stress, or the like, is being or has been exhibited bythe body 701. For example, the pump control system 720, 800 mayperiodically sample or otherwise obtain outputs from the sensingarrangements 706, 708 to obtain values for the characteristics of thebody 701 measured by those sensing arrangements 706, 708, store orotherwise maintain the measured values (e.g., in memory 806), and parseor otherwise analyze the measured values to detect or otherwise identifya condition that is likely to affect the user's insulin response. In theabsence of identifying an insulin sensitivity condition, the closed-loopcontrol adjustment process 900 exits or otherwise terminates and theclosed-loop mode proceeds with the pump control system 720, 800providing closed-loop control to operate the motor 732 and regulate theuser's blood glucose level based on the original control informationstored in the parameter registers 808 in a similar manner as describedabove in the context of FIGS. 4-7.

As described in greater detail below in the context of FIG. 10, inexemplary embodiments, the pump control system 720, 800 periodicallyobtains the user's heart rate measurement data from the heart ratesensing arrangement 706 and analyzes the user's heart rate and heartrate variability to detect or otherwise identify whether the user'sheart rate is indicative of a condition that is likely to affect theuser's insulin response. In this regard, the pump control system 720,800 may detect that the body 701 of the user is experiencing (or hasexperienced) exercise or stress when the user's heart rate is above afirst threshold value (e.g., the heart rate detection threshold) and theuser's heart rate variability is less than a second threshold value(e.g., the heart rate variability detection threshold). For example, thepump control system 720, 800 may detect that the body 701 of the user isexperiencing (or has experienced) exercise or stress when the user'sheart rate exceeds sixty percent of the user's maximum heart rate(HR_(MAX)) for at least a threshold duration of time (e.g., 20 minutes)and the user's heart rate variability decreases by at least a thresholdamount (e.g., by at least twenty-five percent of the user's nominal HRV)over that duration of time.

After identifying that a condition potentially affecting the user'sresponse has occurred, the closed-loop control adjustment process 900continues by identifying or otherwise classifying the identifiedcondition as a particular type of sensitivity condition from among aplurality of conditions that could potentially influence the user'sresponse to the fluid being delivered (task 904). As described ingreater detail below in the context of FIG. 10, after the pump controlsystem 720, 800 detects that the body 701 of the user has experienced aninsulin sensitivity condition based on the user's heart rate measurementdata, the pump control system 720, 800 analyzes the accelerationmeasurement data from the acceleration sensing arrangement 708 toclassify the detected condition as exercise or stress. For example, thepump control system 720, 800 may calculate or otherwise determine anactivity metric associated with the user based on the accelerationmeasurements obtained contemporaneously to the heart rate measurementdata used to identify the insulin sensitivity condition. When themagnitude of the activity metric associated with the body 701 of theuser is greater than an exercise threshold value while the user's heartrate measurements are indicative of an insulin sensitivity condition,the pump control system 720, 800 classifies the detected condition asbeing indicative of exercise. Conversely, when the magnitude of theactivity metric is less than the exercise threshold value, the pumpcontrol system 720, 800 classifies the detected condition as beingindicative of stress.

In some embodiments, the pump control system 720, 800 may also detect orotherwise identify a condition that is likely to influence the user'sinsulin response based on user input received from the user or anotherindividual (e.g., via the CCD 106, the computer 108, and/or a userinterface associated with the infusion device 702 and/or the pumpcontrol system 720). For example, upon entering the closed-loop controlmode, the user may be prompted to identify or otherwise provide inputindicative of whether they have experienced a condition likely toinfluence his or her insulin response and identify the type ofcondition. The pump control system 720, 800 or another component maygenerate or otherwise provide a graphical user interface (GUI) on adisplay associated with the infusion device 702 that includes a list ofconditions likely to influence insulin response with corresponding GUIelements (e.g., buttons, checkboxes, or the like) adapted to allow theuser to select or otherwise indicate which (if any) of the conditionsthe user has experienced over a preceding duration of time (e.g., overthe last 24 hours, since the most recent execution of the closed-loopmode, or the like). In this manner, the pump control system 720, 800 mayreceive a user input (e.g., via communications interface 804 or a userinterface) that indicates or otherwise identifies the type ofcondition(s) likely to influence the user's insulin response that havebeen experienced by the user's body 701 within a preceding interval oftime.

Still referring to FIG. 9, after identifying a condition likely toinfluence a user's response to the fluid being delivered and classifyingthat condition as a particular type of condition, the closed-loopcontrol adjustment process 900 proceeds by automatically adjustingcontrol information for the closed-loop control based on that identifiedtype of insulin sensitivity condition, and thereafter, providingclosed-loop control in accordance with the adjusted control information(tasks 906, 908, 910). In exemplary embodiments, the closed-loop controladjustment process 900 determines one or more adjusted closed-loopcontrol parameters for implementing the closed-loop control mode thataccount for the anticipated change in the user's response for theidentified type of condition (task 906). In this regard, the pumpcontrol system 720, 800 may adjust or otherwise modify values for one ormore gain coefficients, insulin delivery limits, glucose setpoints ortargets, or other control parameters utilized for the closed-loopcontrol mode. For example, in response to detecting exercise, the pumpcontrol system 720, 800 may automatically decrease one or more of thePID gain coefficients to account for the user's anticipated increase ininsulin sensitivity due to exercise, and also, decrease the maximuminsulin infusion rate (e.g., upper insulin delivery limit 559) toaccount for the increase in the user's insulin sensitivity. In one ormore embodiments, the pump control system 720, 800 stores or otherwisemaintains the adjusted values for the control parameters in theparameter registers 808 (e.g., by overwriting the original values in theparameter registers 808). Alternatively, the pump control system 720,800 may multiply the original values in the parameter registers 808 byone or more adjustment factors for the identified condition to obtainadjusted control parameter values for use in the closed-loop PIDcontrol.

In the illustrated embodiment, the closed-loop control adjustmentprocess 900 also determines adjusted configuration information forimplementing the closed-loop control on the identified type of condition(task 908). For example, in one or more embodiments, the pump controlsystem 720, 800 calculates or otherwise determines an adjustedclosed-loop control time limit for providing closed-loop control usingthe adjusted closed-loop control parameters. In some embodiments wherethe closed-loop mode may only be implemented for a specified duration oftime (e.g., 8 hours), based on the identified type of condition, thepump control system 720, 800 may increase or decrease the specifiedduration of time for which the closed-loop mode is allowed to beimplemented before triggering a fail-safe alert and/or transitioning toopen-loop mode (e.g., task 1020). For example, in response to detectingstress or another condition that increases insulin resistance, the pumpcontrol system 720, 800 may reduce the duration of time for which theclosed-loop mode may be provided before the closed-loop mode exitsand/or a fail-safe alert (e.g., fail-safe alert 566) is generated.

In some embodiments, the pump control system 720, 800 determines anadjusted closed-loop control time limit for implementing the adjustedclosed-loop control parameters before reverting to the original (orunadjusted) closed-loop control parameters for the remainder of theclosed-loop mode. For example, if the closed-loop control mode isoriginally configured to generate the fail-safe alert 566 and/or enterthe open-loop mode after eight hours, the pump control system 720, 800determines an adjusted closed-loop control time limit based on theidentified condition that is less than eight hours. Thus, afterproviding closed-loop PID control using the adjusted closed-loop controlparameters for the adjusted closed-loop control time limit, the pumpcontrol system 720, 800 may revert to providing closed-loop PID controlusing the original closed-loop control parameters for the remainder ofthe eight hours before generating the fail-safe alert 566 and/orentering the open-loop mode.

In one or more exemplary embodiments, the pump control system 720, 800identifies or otherwise determines a duration associated with theinsulin sensitivity condition experienced by the user, and determinesthe adjusted closed-loop control time limit based on the duration of thecondition experienced by the user. In this regard, based on timestampsassociated with the heart rate and/or acceleration measurements obtainedfrom sensing arrangements 706, 708, the pump control system 720, 800 maycalculate or otherwise determine the duration of time for which theuser's body 701 was exhibiting the condition. For example, the pumpcontrol system 720, 800 may calculate or otherwise determine a durationfor which the user exercised based on the amount of time that themagnitude of the measured acceleration (or another activity metric)associated with the body 701 of the user is greater than the exercisethreshold value. When the activity metric is less than the exercisethreshold value, the pump control system 720, 800 may calculate orotherwise determine a duration for which the user was experiencingstress based on the amount of time that the user's heart ratevariability was less than the heart rate variability detection thresholdvalue while the user's heart rate was greater than the heart ratedetection threshold. In one or more embodiments, the pump control system720, 800 determines the adjusted closed-loop control time limit in amanner that correlates to the duration of the condition. In this manner,the longer that the user's body 701 experienced the identifiedcondition, the longer the adjusted closed-loop control parameters may beutilized. For example, if the user exercises for one hour, the pumpcontrol system 720, 800 may implement the adjusted closed-loop controlparameters for twice as long as when the user only exercises for thirtyminutes. As described in greater detail below in the context of FIG. 10,the pump control system 720, 800 may also determine the adjusted controlparameters in a manner that is based on or otherwise influenced by theduration of the insulin sensitivity condition.

In some embodiments, the pump control system 720, 800 may identify theduration of the condition based on user input received from the user oranother individual in a similar manner as described above. Afterprompting the user to identify the type of condition(s) that the userexperienced over a preceding time interval, the pump control system 720,800 may prompt the user to input or otherwise provide an estimate of theduration of the condition(s) experienced by the user. For example, inresponse to receiving a user input indicating that the user exercisedtoday, the pump control system 720, 800 may prompt the user to input orotherwise provide the duration of the exercise (e.g., by generating atext box or another GUI element on a display associated with theinfusion device 702). In this manner, the pump control system 720, 800may receive a user input (e.g., via communications interface 804 or auser interface) that indicates or otherwise identifies the durationassociated with the identified type of condition(s) experienced by theuser's body 701 within a preceding interval of time.

Still referring to FIG. 9, after determining the adjusted closed-loopcontrol information based on the identified type of condition, theclosed-loop control adjustment process 900 implements or otherwiseprovides closed-loop control in accordance with the adjusted closed-loopcontrol information (task 910). The pump control system 720, 800utilizes the adjusted gain coefficient(s) and/or insulin limit(s) in theparameter registers 808 (or utilizes the original gain coefficient(s)and/or insulin limit(s) in the parameter registers 808 multiplied byadjustment factor(s)) to generate delivery commands based on a measuredglucose value obtained from the glucose sensing arrangement 704 toregulate the blood glucose level in the body 701 of the user, asdescribed above in the context of FIGS. 4-8. The pump control system720, 800 provides the adjusted closed-loop control until reaching anadjusted closed-loop control time limit or until otherwise determiningthe closed-loop control mode should exit (e.g., task 618). Depending onthe embodiment, the pump control system 720, 800 may provide closed-loopcontrol using the adjusted closed-loop control parameters for a durationof time that is greater than or less than the duration of time for whichthe pump control system 720, 800 would otherwise provide using theoriginal closed-loop control parameters (e.g., in the absence ofidentifying a condition likely to influence the user's insulin responseat task 902).

In some embodiments, the pump control system 720, 800 may provideclosed-loop control using the adjusted closed-loop control parametersfor a duration of time before reverting to the original closed-loopcontrol parameters until generating the fail-safe alert 566 and/orentering the open-loop mode. For example, in response to detectingexercise, the pump control system 720, 800 may provide closed-loopcontrol using decreased PID gain coefficients and an increased upperinsulin limit for the adjusted closed-loop control time limit uponentering the closed-loop mode. After the adjusted closed-loop controltime limit elapses, the pump control system 720, 800 may continue toprovide closed-loop control using the original PID gain coefficients andoriginal upper insulin limit until determining the closed-loop modeshould terminate and entering an open-loop mode and/or generating afail-safe alert 566.

As noted above, in some embodiments, the closed-loop control adjustmentprocess 900 may be performed throughout implementation of theclosed-loop mode (e.g., at each new sampling time) to dynamically adjustthe closed-loop control information to reflect the current condition ofthe user's body 701. In this manner, the closed-loop control adjustmentprocess 900 may dynamically detect a condition likely to influence theuser's insulin response (or sensitivity) in real-time, and in response,dynamically adjust the control information for the closed-loop mode toreflect the current (or instantaneous) condition of the user. Forexample, if the pump control system 720, 800 detects that the user hasbegun exercising while the closed-loop mode is being implemented by thepump control system 720, 800, the pump control system 720, 800 maydynamically update or otherwise adjust one or more of the controlparameters (e.g., one or more gain coefficient(s) and/or insulinlimit(s)) used by the PID control so that the generated deliverycommands for operating the motor 732 to account for the current state ofthe user's body 701. In a similar manner, in some embodiments, theclosed-loop control adjustment process 900 may dynamically detect theabsence of an insulin sensitivity condition, and in response,dynamically restore the control information for the closed-loop mode tothe initial (or original) control information that was implemented uponinitialization of the closed-loop mode. For example, if the pump controlsystem 720, 800 detects that the user's heart rate and/or accelerationmeasurements have fallen below the respective thresholds indicativeexercise, the pump control system 720, 800 may dynamically restore thecontrol parameters (e.g., one or more gain coefficient(s) and/or insulinlimit(s)) used by the PID control to their initial (or original) values.

FIG. 10 depicts an exemplary detection process 1000 suitable forimplementation to automatically detect a condition in the body of theuser that is likely to influence a user's response to a fluid inconjunction with the closed-loop control adjustment process 900 (e.g.,task 902) in the absence of receiving user input identifying thecondition. The various tasks performed in connection with the detectionprocess 1000 may be performed by hardware, firmware, software executedby processing circuitry, or any combination thereof. For illustrativepurposes, the following description refers to elements mentioned abovein connection with FIGS. 1-8. In practice, portions of the detectionprocess 1000 may be performed by different elements of an infusionsystem, such as, for example, an infusion device 702, one or moresensing arrangements 704, 706, 708, and/or a pump control system 720,800. It should be appreciated that the detection process 1000 mayinclude any number of additional or alternative tasks, the tasks neednot be performed in the illustrated order and/or the tasks may beperformed concurrently, and/or the detection process 1000 may beincorporated into a more comprehensive procedure or process havingadditional functionality not described in detail herein. Moreover, oneor more of the tasks shown and described in the context of FIG. 10 couldbe omitted from a practical embodiment of the detection process 1000 aslong as the intended overall functionality remains intact.

In exemplary embodiments, the detection process 1000 begins by obtaininga heart rate measurement associated with the user's body and determiningwhether the heart rate measurement is indicative of a condition that islikely to influence the user's insulin response (tasks 1002, 1004). Inthis regard, the pump control system 720, 800 samples or otherwiseobtains the output of the heart rate sensing arrangement 706 to obtain ameasured heart rate for the body 701 of the user and determines whetherthe measured heart rate is greater than a threshold value indicative theuser's body 701 experiencing exercise or stress. For example, the pumpcontrol system 720, 800 may detect or otherwise identify a conditionlikely to influence the user's insulin response when the measured heartrate value is greater than the user's nominal (or resting) heart ratevalue by more than a threshold percentage (e.g., more than 25% greaterthan the nominal heart rate) or a threshold amount (e.g., more than 2standard deviations of the user's heart rate). For example, in oneembodiment, the pump control system 720, 800 detects exercise when themeasured heart rate value is greater than the user's nominal (orresting) heart rate value by more than sixty percent for more than athreshold duration of time. In an alternative embodiment, the pumpcontrol system 720, 800 detects exercise when the measured heart ratevalue is greater than sixty percent of the user's maximum heart ratevalue for more than a threshold duration of time.

In response to determining the user's heart rate is indicative of apotential insulin sensitivity condition, the detection process 1000continues by obtaining a heart rate variability metric associated withthe user's heart rate and determines whether the heart rate variabilitymetric is also indicative of a condition that is likely to influence theuser's insulin response (tasks 1006, 1008). In accordance with one ormore embodiment, the pump control system 720, 800 calculates orotherwise determines the heart rate variability metric based on heartrate measurements obtained from the user's body 701. For example, thepump control system 720, 800 may buffer, store or otherwise maintainmeasured heart rate values for the user that were obtained over apreceding time interval (e.g., the preceding 5 minutes) and calculatethe user's heart rate variability by performing spectral analysis on themeasured heart rate values. In one embodiment, the pump control system720, 800 calculates the user's heart rate variability as the standarddeviation of the user's measured heart rate values over a preceding oneminute time interval. In yet other embodiments, the heart rate sensingarrangement 706 may determine the heart rate variability and provide theuser's heart rate variability to the pump control system 720, 800 as anoutput from the heart rate sensing arrangement 706.

After obtaining the heart rate variability metric, the pump controlsystem 720, 800 compares the heart rate variability metric to athreshold value indicative of an insulin sensitivity condition. In thisregard, a user's heart rate variability typically decreases during bothexercise and stress relative to the user's nominal heart ratevariability in the absence of an insulin sensitivity condition.Accordingly, in the illustrated embodiment, the pump control system 720,800 detects or otherwise identifies the heart rate variability metric asbeing indicative of exercise or stress when the heart rate variabilitymetric decreases by at least a threshold percentage of the user'snominal heart rate variability (e.g., a 25% decrease in the user's HRV).

In response to determining both the heart rate and the heart ratevariability are indicative of an insulin sensitivity condition, thedetection process 1000 continues by obtaining an activity metricassociated with the user and determining whether the activity metric isindicative of the detected condition being stress or exercise (tasks1010, 1012). In this regard, the pump control system 720, 800 classifiesor otherwise identifies the type for the detected condition (e.g., task904) as being exercise when the activity metric is greater than anexercise threshold value, and conversely, the pump control system 720,800 classifies or otherwise identifies the type for the detectedcondition as being stress when the activity metric is less than theexercise threshold value. In accordance with one or more embodiments,the pump control system 720, 800 calculates or otherwise determines theactivity metric based on acceleration measurements associated with theuser's body 701 that are or were obtained from the acceleration sensingarrangement 708 contemporaneously to the heart rate measurement values.

In a similar manner as described above, the pump control system 720, 800may buffer, store or otherwise maintain the current and previousmeasured acceleration values that were obtained over a preceding timeinterval and calculate the user's activity metric based on thosemeasured acceleration values. For example, the pump control system 720,800 may calculate or otherwise determine an average magnitude ofacceleration for the user's body 701 over the preceding time interval(e.g., the preceding 5 minutes) contemporaneous to the heart ratemeasurements used for determining the heart rate variability metric.When the acceleration is greater than the exercise threshold value overthe preceding time interval where the heart rate measurements indicatestress or exercise, the pump control system 720, 800 classifies orotherwise identifies the detected condition as being exercise.Conversely, when the acceleration is less than the exercise thresholdvalue over the preceding time interval where the heart rate measurementsindicate stress or exercise (e.g., when the user's HRV decreases by atleast 25% relative to the user's nominal HRV), the pump control system720, 800 classifies or otherwise identifies the detected condition asbeing stress.

In response to detecting or otherwise identifying exercise, thedetection process 1000 continues by adjusting the closed-loop controlinformation (e.g., tasks 906, 908) to compensate for exercise (task1014). In this regard, an increase in physical activity amplifiesglucose uptake by the working tissues. For non-diabetic persons, glucosehomeostasis is maintained by lowering endogenous insulin secretion andincreasing hepatic glucose production due to elevated glucagon andcatecholamine levels. For type 1 diabetic mellitus (T1DM) patients, theabove-mentioned hormonal adaptation during elevated physical activity isgreatly diminished. As a result, presence of high levels of exogenousinsulin in the circulation may prevent mobilization of glucose duringexercise causing hypoglycemia. Conversely, too little insulin in thecirculation may result in excessive release of counter-insulin hormonesduring exercise which may cause hyperglycemia.

Based on the intensity and duration of exercise detected by the pumpcontrol system 720, 800, the amount of energy expenditure (AEE) duringexercise can be determined by the following equation: AEE=MET×RMR×BW×D,where RMR is the resting metabolic rate in kilocalories (kcal) perkilogram per hour (which is a function of the body weight, age, height,and gender), MET is a multiplier (scaling factor) for the metabolicequivalent task representing the intensity of the exercise, BW is bodyweight in kilograms, and D is the duration of exercise in hours. Duringa resting period, MET=1.0, and resting energy expenditure can bedetermined by the following equation: AEE_(R)=RMR×BW×D. Therefore, therelative AEE (AEE) can be obtained as AEE=AEE−AEE_(R). Glycemic levelchanges for T1DM patients due to exercise can be written as ΔG=G_(F)−G₀,where G_(F) is the glucose concentration (mg/dL) after exercise and G₀is the glucose concentration (mg/dL) before exercise.

By way of example, the relationship between the change in glucose level(ΔG) and exercise can be mathematically represented by the followingequation: ΔG=f_(1E)×AEE(IOB₁−IOB), where IOB₁ is the idealinsulin-on-board (U) at elevated activity level, IOB is the actualinsulin-on-board (U), and f_(1E) is the activity insulin equivalentfactor. If IOB is equal to IOB₁ then the net ΔG will be equal to zero,indicating an ideal plasma insulin level during exercise thereby causinga perfect glucose homeostasis (no change) which is usually the case fornon-diabetics. On the other hand, IOB<IOB₁ will cause a positive ΔG(elevated glucose level in post-exercise period), and IOB>IOB₁ willcause a negative ΔG (reduced glucose level in post-exercise period)which is the most predominant scenario for T1DM patients. The drop inglucose concentration due to physical activity (e.g., when ΔG<0) can beconverted to an equivalent insulin amount (I_(EQ)) in units (U) by usingthe patient's insulin sensitivity factor (SI in mg/dL/U) as follows:I_(EQ)=|ΔG/SI|.

In accordance with one or more embodiments, in response to detectingexercise, an adjusted reduced proportional gain coefficient (K_(P)*) maybe calculated by estimating the amount of energy expenditure,calculating the change in glycemic level, and determining the equivalentinsulin amount before using the equation:

${K_{P}^{*} = {\frac{60}{90} \times \frac{{DIR} - I_{EQ}}{1500}}},$where DIR is the daily insulin requirement in units (U).

In accordance with one or more embodiments, in response to detectingexercise, an adjusted increased glucose target (or setpoint) for theclosed-loop control is calculated when ΔG<0 using the equation:G_(T)*=G_(T)+k×|ΔG|, where G_(T) is the nominal glucose target, G_(T)*is the adjusted glucose target, and k is a scaling factor between zeroand one. In this regard, the scaling factor influences the amount orrate of adjustment for the glucose target, where increasing the value ofk increases the amount or rate of adjustment and decreasing the value ofk decreases the amount or rate of adjustment. In some embodiments, thevalue of k may be fixed or predetermined when the infusion device 700 isdeployed. In other embodiments, the value of k may be set or otherwiseadjusted by a user, such as a doctor or the patient. In yet otherembodiments, the value of k may be dynamically determined based on theuser's historical response to exercise that is observed over thelifetime of the infusion device 700. In this regard, the value of thescaling factor may be dynamically adjusted to account for changes in theuser's observed response to exercise as the user ages, experienceslifestyle changes, or the like.

In exemplary embodiments, in response to detecting exercise, an adjustedupper insulin delivery limit is also calculated to compensate forchanges to the user's insulin response (or sensitivity). The deliverylimit is calculated based on the patient's basal rate, fasting bloodglucose, and insulin sensitivity. Examination of the post night fastingblood glucose (FBG) levels allows an estimate of a single FBG value(FBG₀) that is a function of the overnight basal insulin (I_(basal,0)).Having estimated FBG₀, its corresponding I_(basal,0), and KI, anestimate of the insulin maximum delivery rate (U_(max)) can be made.Thus, if the delivery of insulin were to occur at the U_(max), thiswould result in a fasting blood glucose level defined by BG_(LBL), whichis the lower buffer limit. U_(max) is calculated by the followingequation:

${U_{\max} = {I_{{basal},0} + \frac{{BG}_{LBL} - {FBG}_{0}}{KI}}},$where

${KI} = {{- 3} \times {\frac{1800}{DIR}.}}$

In accordance with one embodiment, in response to detecting exercise,when ΔG<0, an adjusted estimated fasting blood glucose value iscalculated using the equation FBG₀*=FBG₀+ΔG and an adjusted upperinsulin limit (U_(max)*) is calculated based on the adjusted estimatedfasting blood glucose value using the equation:

$U_{\max}^{*} = {I_{{basal},0} + {\frac{{BG}_{LBL} - {FBG}_{0}^{*}}{KI}.}}$In an alternative embodiment, in response to detecting exercise, anadjusted daily insulin requirement is calculated using equationDIR*=DIR−I_(EQ), an adjusted and the adjusted upper insulin limit iscalculated using the equation

${U_{\max}^{*} = {I_{{basal},0} + \frac{{BG}_{LBL} - {FBG}_{0}}{{KI}^{*}}}},$where

${KI}^{*} = {{- 3} \times {\frac{1800}{{DIR}^{*}}.}}$In accordance with yet another embodiment, in response to detectingexercise, the adjusted upper insulin delivery limit is chosen to beequal to the overnight basal insulin (I_(basal,0)).

Exercise can have has a prolonged effect on the insulin sensitivity, andtherefore, in exemplary embodiments, in addition to adjusting thecontrol parameters (e.g., K_(P)*, G_(T)*, U_(max)*), the pump controlsystem 720, 800 calculates or otherwise determines an adjustedclosed-loop control time limit (e.g., task 908) as a function of theduration of the exercise and the intensity. In this regard, the adjustedclosed-loop control time limit ensures that the adjusted closed-loopcontrol parameters are implemented for a sufficiently long duration oftime to account for the anticipated prolonged effect of the exercise onthe user's insulin response based on the duration and intensity of theexercise.

Still referring to FIG. 10, in response to detecting or otherwiseidentifying stress, the detection process 1000 continues by adjustingthe closed-loop control information (e.g., tasks 906, 908) to compensatefor stress (task 1016). Under stress the body behaves as if it is underattack, and it prepares itself to take action, which is commonly knownas the fight-or flight response. Under such a condition, the hormonelevels are significantly elevated. The net effect is to make a lot ofstored energy (e.g., glucose and fat) available to the cells in order totake necessary action. For T1DM patients, the stress induced elevatedlevels of glucose cannot be metabolized properly due to lack of insulin.As a result, majority of T1DM patients experience stress induced chronichyperglycemia. However, studies have also reported that some T1DMpatients might even undergo hypoglycemia due to stress.

In accordance with one embodiment, the effect of stress on blood glucoseconcentration is estimated using the equation: ΔG=f_(STRESS)×S_(I),where f_(STRESS) is a stress scaling factor, S_(I) is an estimate of thestress intensity, and ΔG is the change in glucose level before and afterstress. The stress scaling factor (f_(STRESS)) maps the stress intensityto the user's change in glucose level. In exemplary embodiments, thestress scaling factor is patient-specific and will be positive forpatients that experience hyperglycemia due to stress and negative forpatients that experience hypoglycemia due to stress. The pump controlsystem 720, 800 calculates or otherwise determines the stress intensity(S_(I)) based on the user's heart rate variability. In this regard, thestress intensity (S_(I)) may correspond to the amount of the decrease inthe user's heart rate variability (e.g., a greater decrease correspondsto a greater stress intensity) and/or the duration of time over whichthe user's heart rate variability decreased (e.g., a greater duration ofdecreased heart rate variability corresponds to a greater stressintensity).

In a similar manner as described above in the context of exercise, afteran estimated change in glucose level is determined, an equivalentinsulin amount (I_(EQ)) can be determined based on the estimated changein glucose level, and an adjusted proportional gain coefficient iscalculated as

${K_{P}^{*} = {\frac{60}{90} \times \frac{{DIR} + I_{EQ}}{1500}}},$where I_(EQ)=ΔG/SI. In this regard, when ΔG>0, the adjusted proportionalgain coefficient is increased relative to the initial (or unadjustedoriginal) proportional gain coefficient. An adjusted decreased glucosetarget (or setpoint) for the closed-loop control may also be calculatedwhen ΔG>0 using the equation: G_(T)*=G_(T)−k×ΔG. Additionally, anadjusted upper insulin limit (U_(max)*) is calculated based on theadjusted estimated fasting blood glucose value using the equation:

${U_{\max}^{*} = {I_{{basal},0} + \frac{{BG}_{LBL} - {FBG}_{0}^{*}}{KI}}},$where FBG₀*=FBG₀+ΔG. In this regard, when ΔG>0, the adjusted upperinsulin limit is increased relative to the initial (or unadjustedoriginal) upper insulin limit (e.g., U_(max)*>U_(max)). In analternative embodiment, in response to detecting stress, an adjusteddaily insulin requirement is calculated using an adjusted daily insulinrequirement as described above (e.g., DIR*=DIR+I_(EQ), whereI_(EQ)=ΔG/SI). In one or more embodiments, in addition to adjusting thecontrol parameters, the pump control system 720, 800 calculates orotherwise determines an adjusted closed-loop control time limit (e.g.,task 908) as a function of the duration of the stress and the stressintensity to account for the anticipated duration for the stress'simpact on the user's insulin response.

To briefly summarize, the subject matter described herein allows for aninsulin sensitivity condition, such as exercise or stress, to beautomatically detected and classified as a particular type of insulinsensitivity condition based on characteristics associated with theuser's body (e.g., heart rate measurements, acceleration measurements,or the like). In response to detecting and classifying an insulinsensitivity condition, closed-loop control information used whenproviding closed-loop control of the user's blood glucose level isautomatically adjusted based on the identified insulin sensitivitycondition to account for the anticipated changes in the user's insulinresponse. One or more PID gain coefficients, insulin delivery limits,setpoints or targets, and/or other control parameters used to generateinsulin delivery commands may be automatically adjusted to compensatefor the changes in the user's insulin sensitivity. Additionally,configuration information (e.g., time limits or the like) utilized inproviding closed-loop control may also be automatically adjusted. Thus,the user's blood glucose level may be more effectively managed usingclosed-loop control in a manner that does not require a user or anotherindividual (e.g., the user's doctor, nurse, caretaker, or the like) tomanually adjust the control information on a daily basis to account forthe user's daily activities. Additionally, in some embodiments, theclosed-loop control information may be dynamically adjusted in real-timeto account for the current state of the user when the user beginsexperiencing an insulin sensitivity condition while closed-loop controlmode is being provided.

For the sake of brevity, conventional techniques related to glucosesensing and/or monitoring, sensor calibration and/or compensation, andother functional aspects of the subject matter may not be described indetail herein. In addition, certain terminology may also be used in theherein for the purpose of reference only, and thus is not intended to belimiting. For example, terms such as “first,” “second,” and other suchnumerical terms referring to structures do not imply a sequence or orderunless clearly indicated by the context. The foregoing description mayalso refer to elements or nodes or features being “connected” or“coupled” together. As used herein, unless expressly stated otherwise,“coupled” means that one element/node/feature is directly or indirectlyjoined to (or directly or indirectly communicates with) anotherelement/node/feature, and not necessarily mechanically.

While at least one exemplary embodiment has been presented in theforegoing detailed description, it should be appreciated that a vastnumber of variations exist. It should also be appreciated that theexemplary embodiment or embodiments described herein are not intended tolimit the scope, applicability, or configuration of the claimed subjectmatter in any way. For example, the subject matter described herein isnot limited to the infusion devices and related systems describedherein. Moreover, the foregoing detailed description will provide thoseskilled in the art with a convenient road map for implementing thedescribed embodiment or embodiments. It should be understood thatvarious changes can be made in the function and arrangement of elementswithout departing from the scope defined by the claims, which includesknown equivalents and foreseeable equivalents at the time of filing thispatent application. Accordingly, details of the exemplary embodiments orother limitations described above should not be read into the claimsabsent a clear intention to the contrary.

What is claimed is:
 1. A method of operating an infusion devicecomprising a motor operable to deliver a fluid to a user, the methodcomprising: identifying a condition of the user that is likely toinfluence a response to the fluid in a body of the user; classifying thecondition as exercise; and after classifying the condition as exercise:estimating an amount of energy expenditure during the exercise;calculating a change in glycemic level for the user based on the amountof energy expenditure; determining an equivalent insulin amount based onthe change in glycemic level; determining an adjusted proportional gaincoefficient based on a first difference between a daily insulinrequirement for the user and the equivalent insulin amount; determininga delivery command by applying the adjusted proportional gaincoefficient to a second difference between a measured glucose valueobtained from a glucose sensing arrangement and a target blood glucose;and operating the motor of the infusion device in accordance with thedelivery command to deliver the fluid to the user in accordance with theadjusted proportional gain coefficient.
 2. The method of claim 1,further comprising obtaining a heart rate measurement associated withthe user, wherein identifying the condition comprises detecting thecondition when the heart rate measurement is greater than a firstthreshold value and a variability metric associated with the heart ratemeasurement is less than a second threshold value.
 3. The method ofclaim 2, further comprising obtaining an activity metric associated withthe user, wherein classifying the condition comprises: classifying thecondition as exercise when the activity metric is greater than anexercise threshold value.
 4. The method of claim 3, wherein determiningthe adjusted proportional gain coefficient comprises decreasing aproportional gain coefficient in response to classifying the conditionas exercise.
 5. The method of claim 1, further comprising increasing adelivery limit in response to classifying the condition as exercise,wherein determining the delivery command comprises determining thedelivery command using the adjusted proportional gain coefficient inaccordance with the adjusted delivery limit.
 6. The method of claim 1,wherein: identifying the condition comprises identifying a sensitivitycondition when a heart rate measurement associated with the user isgreater than a first threshold value and a variability metric associatedwith the heart rate measurement is less than a second threshold value;and classifying the condition comprises classifying the sensitivitycondition as exercise based on an activity metric associated with theuser relative to a third threshold value.
 7. A method of operating aninfusion device comprising a motor operable to deliver a fluid to auser, the method comprising: identifying a condition of the user that islikely to influence a response to the fluid in a body of the user;classifying the condition as stress; and in response to classifying thecondition as stress: estimating a change in glycemic level for the userbased at least in part on an intensity of the stress; determining anequivalent insulin amount based on the change in glycemic level; anddetermining an adjusted proportional gain coefficient based on a firstdifference between a daily insulin requirement for the user and theequivalent insulin amount; and determining a delivery command byapplying the adjusted proportional gain coefficient to a seconddifference between a measured glucose value obtained from a glucosesensing arrangement and a target blood glucose; and operating the motorof the infusion device in accordance with the delivery command.
 8. Themethod of claim 7, wherein determining the adjusted proportional gaincoefficient comprises increasing a proportional gain coefficient inresponse to classifying the condition as stress.
 9. The method of claim7, further comprising decreasing a delivery limit in response toclassifying the condition as stress, wherein determining the deliverycommand comprises determining the delivery command using the adjustedproportional gain coefficient in accordance with the adjusted deliverylimit.
 10. A method of operating an infusion device capable ofdelivering insulin to a user, the method comprising: obtaining heartrate measurement data for the user using a heart rate sensingarrangement; identifying an insulin sensitivity condition based on theheart rate measurement data when a heart rate associated with the useris greater than a first threshold and a heart rate variabilityassociated with the user is less than a second threshold value;obtaining an activity metric for the user; classifying the insulinsensitivity condition as stress when the activity metric is less than athird threshold value; and after classifying the insulin sensitivitycondition as stress: automatically adjusting control information foroperating the infusion device to account for an anticipated increase inthe user's insulin resistance based on the stress, resulting in adjustedcontrol information; determining one or more delivery commands foroperating a motor of the infusion device in accordance with the adjustedcontrol information; and operating the motor to deliver the insulin tothe user in accordance with the one or more delivery commands.
 11. Themethod of claim 10, wherein automatically adjusting control informationcomprises automatically increasing an insulin infusion rate upper limit.12. The method of claim 10, wherein automatically adjusting controlinformation comprises decreasing a target glucose setpoint valueutilized for providing closed-loop control of a glucose level of theuser.
 13. The method of claim 10, wherein automatically adjustingcontrol information comprises increasing a gain coefficient utilized forproviding closed-loop control of a glucose level of the user.
 14. Themethod of claim 10, further comprising estimating an effect of thestress using the equation ΔG=f_(STRESS)×S_(I), where f_(STRESS) is astress scaling factor, S_(I) is an estimate of stress intensity, and ΔGis a change in glucose level before and after stress, whereinautomatically adjusting control information comprises calculating anadjusted proportional gain coefficient (K_(P)*) using the equation${K_{P}^{*} = {\frac{60}{90} \times \frac{{DIR} + I_{EQ}}{1500}}},$where DIR is a daily insulin requirement for the user, I_(EQ)=ΔG/SI, andSI is an insulin sensitivity factor for the user.
 15. The method ofclaim 14, further comprising determining the estimate of stressintensity based on the heart rate variability.
 16. The method of claim10, further comprising estimating an effect of the stress using theequation ΔG=f_(STRESS)×S_(I), where f_(STRESS) is a stress scalingfactor, S_(I) is an estimate of stress intensity, and ΔG is a change inglucose level before and after stress, wherein automatically adjustingcontrol information comprises calculating a decreased glucose target(G_(T)*) using the equation G_(T)*=G_(T)−k×ΔG, where k is a scalingfactor.
 17. The method of claim 10, further comprising estimating aneffect of the stress using the equation ΔG=f_(STRESS)×S_(I), wheref_(STRESS) is a stress scaling factor, S_(I) is an estimate of stressintensity, and ΔG is a change in glucose level before and after stress,wherein automatically adjusting control information comprisescalculating an adjusted upper insulin limit (U_(max)*) using equation${U_{{ma}\; x}^{*} = {I_{{basal},0} + \frac{{BG}_{LBL} - {FBG}_{0}^{*}}{KI}}},$where I_(basal,0) is an overnight basal insulin for the user, BG_(LBL) afasting glucose level corresponding to a maximum delivery rate,${{KI} = {{- 3} \times \frac{1800}{DIR}}},$ DIR is a daily insulinrequirement for the user, FBG₀*=FBG₀+ΔG, and FBG₀ is an estimate of thefasting glucose level corresponding to the overnight basal insulin. 18.The method of claim 10, further comprising estimating an effect of thestress using the equation ΔG=f_(STRESS)×S_(I), where f_(STRESS) is astress scaling factor, S_(I) is an estimate of stress intensity, and ΔGis a change in glucose level before and after stress, whereinautomatically adjusting control information comprises calculating anadjusted daily insulin requirement (DIR*) using the equationDIR*=DIR+I_(EQ), where I_(EQ)=ΔG/SI and DIR is a daily insulinrequirement for the user.
 19. The method of claim 10, whereinautomatically adjusting control information for operating the infusiondevice comprises determining an adjusted closed-loop control time limitas a function of a duration of the stress and an intensity of thestress.